Researcher Profile and Settings

Affiliation

• Faculty of Veterinary Medicine　Veterinary Medicine　Basic Veterinary Sciences

Job Title

• Associate Professor

Degree

• D.V.M.Ph.D.（Hokkaido University）

URL

http://www.vetmed.hokudai.ac.jp/organization/anat/index.html

Research funding number

• 60547769

J-Global ID

• 200901045319589831

Research Interests

• CKD   Autoimmune disease   Renal pathology   IL-36   Podocyte injury   レーザーマイクロダイセクション   電子顕微鏡   腎生検   exosome   biomarker   尿   慢性腎臓病   microRNA   モデルマウス   伴侶動物   疾患モデルマウス   慢性糸球体腎炎   犬   腎疾患   猫   マウス   ネコ   イヌ   糸球体   自己免疫   miRNA   腎臓   分子形態学   獣医解剖学   

Research Areas

• Life sciences / Allergies and connective tissue disease
• Life sciences / Urology
• Life sciences / Zoological sciences
• Life sciences / Morphology, anatomy
• Life sciences / Nephrology
• Life sciences / Anatomy
• Life sciences / Veterinary medicine

Academic & Professional Experience

• 2017/04 - Today Faculty of Veterinary Medicine, Hokkaido University Division of Basic Veterinary Science, Laboratory of Anatomy Associate professor
• 2014/04 - 2017/03 Hokkaido University Graduate school of veterinary medicine Associate professor
• 2009/04 - 2014/03 Hokkaido University Graduate School of Veterinary Medicine
• 2011/09 - 2012/08 NIH NIDDK 腎臓病研究部門 リサーチフェロー
• 2007/04 - 2009/03 Hokkaido University Graduate School of Veterinary Medicine

Education

•        - 2009  Hokkaido University  Graduate School of Veterinary Medicine  Veterinary Medicine
•        - 2006  Kagoshima University  Faculty of Agriculture  Veterinary Medicine

Association Memberships

• 日本解剖学会   日本獣医腎泌尿器学会   日本獣医学会   

Research Activities

Published Papers

• Suppurative Osteomyelitis Incorrectly Diagnosed as Rheumatoid Arthritis.

  Taro Horino, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 26 (7) e261-e263  2020/10 [Refereed][Not invited]
  
• Anatomy and histology of the foramen of ovarian bursa opening to the peritoneal cavity and its changes in autoimmune disease-prone mice.

  Marina Hosotani, Osamu Ichii, Teppei Nakamura, Takashi Namba, Md Rashedul Islam, Yaser Hosny Ali Elewa, Takafumi Watanabe, Hiromi Ueda, Yasuhiro Kon

  Journal of anatomy 2020/09/01 [Refereed][Not invited]
   

  The ovarian bursa is a small peritoneal cavity enclosed by the mesovarium and mesosalpinx, which surrounds the ovaries and oviductal infundibulum in mammals. The ovarian bursa is considered as the structure facilitating the transport of ovulated oocytes into the oviduct. Our previous study revealed reduced oocyte pick-up function in the oviduct of lupus-prone MRL/MpJ-Faslpr/lpr mouse, suggesting the possibility of an escape of ovulated oocytes into the peritoneal cavity, despite the presence of an almost complete ovarian bursa in the mouse. In this study, we revealed anatomical and histological characteristics of the ovarian bursa in C57BL/6 N, MRL/MpJ, and MRL/MpJ-Faslpr/lpr mice. All strains had the foramen of ovarian bursa (FOB), with a size of approximately 0.04 to 0.12 cm2 , surrounded by the ligament of ovarian bursa (LOB), which is part of the mesosalpinx. The LOB was partially lined with the cuboidal mesothelial cells and consisted of a thick smooth muscle layer in all strains. In 6-month-old MRL/MpJ-Faslpr/lpr mice, in which the systemic autoimmune abnormality deteriorated and oocyte pick-up function was impaired, the size of the FOB tended to be larger than that of other strains. Additionally, in MRL/MpJ-Faslpr/lpr mice at 6 months of age, there was infiltration by numerous immune cells in the mesosalpinx suspending the isthmus; however, the LOB prevented severe inflammation and showed deposition of collagen fibers. These results not only indicate that the FOB is a common structure within mice, but also imply the physiological function of the LOB and its role in maintaining the microenvironment around the ovary, as well as regulating healthy reproduction.
• Antineutrophil Cytoplasmic Antibody-Associated Hypertrophic Pachymeningitis Mimicking Petroclival Meningioma.

  Taro Horino, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 26 (6) e153-e154  2020/09 [Refereed][Not invited]
  
• Long-term Imaging Findings on Serial FDG PET/CT Scans in a Patient With Polymyositis.

  Taro Horino, Tatsuki Matsumoto, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 26 (6) e174-e175  2020/09 [Refereed][Not invited]
  
• Hydroxychloroquine-Associated Hyperpigmentation in Chilblain Lupus Erythematosus.

  Taro Horino, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 26 (6) e192  2020/09 [Refereed][Not invited]
  
• Anomalous Inferior Vena Cava in a Patient With Limited Cutaneous Systemic Sclerosis and Primary Biliary Cholangitis.

  Taro Horino, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 26 (6) e203  2020/09 [Refereed][Not invited]
  
• Takayasu Arteritis Presenting as Renovascular Hypertension.

  Taro Horino, Osamu Ichii, Tatsuki Matsumoto, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 26 (5) e94  2020/08 [Refereed][Not invited]
  
• Altered hepatic cytochrome P450 expression in cats after chronic exposure to decabromodiphenyl ether (BDE-209).

  Kraisiri Khidkhan, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M M Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  The Journal of veterinary medical science 82 (7) 978 - 982 2020/07/31 [Refereed][Not invited]
   

  The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.
• Comparative Analyses of the Antiviral Activities of IgG and IgA Antibodies to Influenza A Virus M2 Protein.

  Kosuke Okuya, Nao Eguchi, Rashid Manzoor, Reiko Yoshida, Shinji Saito, Tadaki Suzuki, Michihito Sasaki, Takeshi Saito, Yurie Kida, Akina Mori-Kajihara, Hiroko Miyamoto, Osamu Ichii, Masahiro Kajihara, Hideaki Higashi, Ayato Takada

  Viruses 12 (7) 2020/07/20 [Refereed][Not invited]
   

  The influenza A virus (IAV) matrix-2 (M2) protein is an antigenically conserved viral envelope protein that plays an important role in virus budding together with another envelope protein, hemagglutinin (HA). An M2-specific mouse monoclonal IgG antibody, rM2ss23, which binds to the ectodomain of the M2 protein, has been shown to be a non-neutralizing antibody, but inhibits plaque formation of IAV strains. In this study, we generated chimeric rM2ss23 (ch-rM2ss23) IgG and IgA antibodies with the same variable region and compared their antiviral activities. Using gel chromatography, ch-rM2ss23 IgA were divided into three antibody subsets: monomeric IgA (m-IgA), dimeric IgA (d-IgA), and trimeric and tetrameric IgA (t/q-IgA). We found that t/q-IgA had a significantly higher capacity to reduce the plaque size of IAVs than IgG and m-IgA, most likely due to the decreased number of progeny virus particles produced from infected cells. Interestingly, HA-M2 colocalization was remarkably reduced on the infected cell surface in the presence of ch-rM2ss23 antibodies. These results indicate that anti-M2 polymeric IgA restricts IAV budding more efficiently than IgG and suggest a role of anti-M2 IgA in cross-protective immunity to IAVs.
• Antineutrophil cytoplasmic antibody-associated vasculitis in diffuse large B cell lymphoma.

  Taro Horino, Osamu Ichii

  Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia 2020/07/18 [Refereed][Not invited]
  
• Hepatitis C Virus-Associated Cryoglobulinemic Vasculitis.

  Taro Horino, Osamu Ichii, Satoshi Inotani, Tatsuki Matsumoto, Yoshio Terada

  The American journal of medicine 133 (7) e367-e368  2020/07 [Refereed][Not invited]
  
• Activities of matrix metalloproteinase-2, matrix metalloproteinase-9, and serine proteases in samples of the colorectal mucosa of Miniature Dachshunds with inflammatory colorectal polyps.

  Noriyuki Nagata, Hiroshi Ohta, Arisa Yamada, Yong Bin Teoh, Osamu Ichii, Keitaro Morishita, Noboru Sasaki, Mitsuyoshi Takiguchi

  American journal of veterinary research 81 (7) 572 - 580 2020/07 [Refereed][Not invited]
   

  OBJECTIVE: To investigate the activities of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) and serine proteases in the colorectal mucosa of Miniature Dachshunds (MDs) with inflammatory colorectal polyps (ICRPs). ANIMALS: 15 MDs with ICRPs and 5 dogs with non-ICRP-related large bowel diarrhea (controls). PROCEDURES: Zymographic methods were used to evaluate the activities of MMP-2, MMP-9, latent forms of MMP-2 and MMP-9 (pro-MMP-2 and pro-MMP-9), and serine proteases in inflamed and noninflamed tissue samples from MDs with ICRPs and in noninflamed tissue samples from control dogs. The associations of serine protease activities with MMP-2 or MMP-9 activity were also analyzed. RESULTS: Activities of pro-MMP-2 and pro-MMP-9 were detected in most tissue samples, regardless of the tissue type, whereas activities of MMP-2 and MMP-9 were not detected in control tissue samples. In the inflamed tissue samples from MDs with ICRPs, the activities of MMP-2, pro-MMP-9, and MMP-9 were significantly higher than those in the noninflamed tissue samples from those dogs. Serine protease activities were significantly higher in the inflamed and noninflamed tissue samples from MDs with ICRP, compared with findings for control tissue samples. A weak correlation was detected between serine protease activities and MMP-9 activity. CONCLUSIONS AND CLINICAL RELEVANCE: Study results suggested that gelatinase and serine protease activities are upregulated in the colorectal mucosa of MDs with ICRPs, possibly contributing to the pathogenesis of this disease through the functions of these enzymes in degradation of extracellular matrix and promotion of inflammatory cell migration and inflammatory responses.
• BXSB/MpJ-Yaa mouse model of systemic autoimmune disease shows increased apoptotic germ cells in stage XII of the seminiferous epithelial cycle.

  Yuki Otani, Osamu Ichii, Md Abdul Masum, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Cell and tissue research 381 (1) 203 - 216 0302-766X 2020/07 [Refereed][Not invited]
   

  In mammals, the reproductive system and autoimmunity regulate mutual functions. Importantly, systemic autoimmune diseases are thought to cause male infertility but the underlying pathological mechanism remains unclear. In this study, the morpho-function of the testes in BXSB/MpJ-Yaa mice was analyzed as a representative mouse model for systemic autoimmune diseases to investigate the effect of excessive autoimmunity on spermatogenesis. At 12 and 24 weeks of age, BXSB/MpJ-Yaa mice showed splenomegaly and increased levels of serum autoantibodies, whereas no controls showed a similar autoimmune condition. In histological analysis, the enlarged lumen of the seminiferous tubules accompanied with scarce spermatozoa in the epididymal ducts were observed in some of the BXSB/MpJ-Yaa and BXSB/MpJ mice but not in C57BL/6N mice. Histoplanimetrical analysis revealed significantly increased residual bodies and apoptotic germ cells in the seminiferous tubules in BXSB/MpJ-Yaa testes without apparent inflammation. Notably, in stage XII of the seminiferous epithelial cycles, the apoptotic germ cell number was remarkably increased, showing a significant correlation with the indices of systemic autoimmune disease in BXSB/MpJ-Yaa mice. Furthermore, the Sertoli cell number was reduced at the early disease stage, which likely caused subsequent morphological changes in BXSB/MpJ-Yaa testes. Thus, our histological study revealed the altered morphologies of BXSB/MpJ-Yaa testes, which were not observed in controls and statistical analysis suggested the effects of an autoimmune condition on this phenotype, particularly the apoptosis of meiotic germ cells. BXSB/MpJ-Yaa mice were shown to be an efficient model to study the relationship between systemic autoimmune disease and the local reproductive system.
• Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease.

  Masaya Hiraishi, Md Abdul Masum, Takashi Namba, Yuki Otani, Yaser Ha Elewa, Osamu Ichii, Yasuhiro Kon

  Experimental biology and medicine (Maywood, N.J.) 245 (12) 999 - 1008 2020/06 [Refereed][Not invited]
   

  IMPACT STATEMENT: Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjögren's syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease.
• Potential Role of Nonneutralizing IgA Antibodies in Cross-Protective Immunity against Influenza A Viruses of Multiple Hemagglutinin Subtypes.

  Kosuke Okuya, Reiko Yoshida, Rashid Manzoor, Shinji Saito, Tadaki Suzuki, Michihito Sasaki, Takeshi Saito, Yurie Kida, Akina Mori-Kajihara, Tatsunari Kondoh, Masahiro Sato, Masahiro Kajihara, Hiroko Miyamoto, Osamu Ichii, Hideaki Higashi, Ayato Takada

  Journal of virology 94 (12) 2020/06/01 [Refereed][Not invited]
   

  IgA antibodies on mucosal surfaces are known to play an important role in protection from influenza A virus (IAV) infection and are believed to be more potent than IgG for cross-protective immunity against IAVs of multiple hemagglutinin (HA) subtypes. However, in general, neutralizing antibodies specific to HA are principally HA subtype specific. Here, we focus on nonneutralizing but broadly cross-reactive HA-specific IgA antibodies. Recombinant IgG, monomeric IgA (mIgA), and polymeric secretory IgA (pSIgA) antibodies were generated based on the sequence of a mouse anti-HA monoclonal antibody (MAb) 5A5 that had no neutralizing activity but showed broad binding capacity to multiple HA subtypes. While confirming that there was no neutralizing activity of the recombinant MAbs against IAV strains A/Puerto Rico/8/1934 (H1N1), A/Adachi/2/1957 (H2N2), A/Hong Kong/483/1997 (H5N1), A/shearwater/South Australia/1/1972 (H6N5), A/duck/England/1/1956 (H11N6), and A/duck/Alberta/60/1976 (H12N5), we found that pSIgA, but not mIgA and IgG, significantly reduced budding and release of most of the viruses from infected cells. Electron microscopy demonstrated that pSIgA deposited newly produced virus particles on the surfaces of infected cells, most likely due to tethering of virus particles. Furthermore, we found that pSIgA showed significantly higher activity to reduce plaque sizes of the viruses than IgG and mIgA. These results suggest that nonneutralizing pSIgA reactive to multiple HA subtypes may play a role in intersubtype cross-protective immunity against IAVs.IMPORTANCE Mucosal immunity represented by pSIgA plays important roles in protection from IAV infection. Furthermore, IAV HA-specific pSIgA antibodies are thought to contribute to cross-protective immunity against multiple IAV subtypes. However, the mechanisms by which pSIgA exerts such versatile antiviral activity are not fully understood. In this study, we generated broadly cross-reactive recombinant IgG and pSIgA having the same antigen-recognition site and compared their antiviral activities in vitro These recombinant antibodies did not show "classical" neutralizing activity, whereas pSIgA, but not IgG, significantly inhibited the production of progeny virus particles from infected cells. Plaque formation was also significantly reduced by pSIgA, but not IgG. These effects were seen in infection with IAVs of several different HA subtypes. Based on our findings, we propose an antibody-mediated host defense mechanism by which mucosal immunity may contribute to broad cross-protection from IAVs of multiple HA subtypes, including viruses with pandemic potential.
• Altered ciliary morphofunction in the oviductal infundibulum of systemic autoimmune disease-prone MRL/MpJ-Faslpr/lpr mice.

  Marina Hosotani, Osamu Ichii, Teppei Nakamura, Md Abdul Masum, Yuki Otani, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Cell and tissue research 380 (3) 627 - 641 2020/06 [Refereed][Not invited]
   

  According to our previous reports, impaired oocyte pickup was observed in the oviductal infundibulum of an autoimmune disease (AD) mouse model, suggesting a relationship between female infertility and AD. This study examines the relationship between AD and infundibulum morphofunction by focusing on the epithelial cilia. Healthy MRL/MpJ and AD-prone MRL/MpJ-Faslpr/lpr mice were examined at 3 and 6 months of age, representing early and late disease stages, respectively. Oocyte pickup indices decreased with AD progression indicated by splenomegaly, autoantibody production and increased T cell counts of infundibulum mucosa in MRL/MpJ-Faslpr/lpr mice. Ciliary beating frequency (CBF) and height in the infundibulum were faster and higher in MRL/MpJ-Faslpr/lpr mice than in MRL/MpJ mice at the early AD stages, although the absolute CBF values were lower at the late AD stage. At the late stage, ciliary height did not differ between mouse lines but the morphological index of cilia beating direction indicated randomized patterns in MRL/MpJ-Faslpr/lpr mice. The tracheal mucosa was also examined as a representative example of cilia morphology; its CBF decreased at the late AD stage in MRL/MpJ-Faslpr/lpr; however, there were no AD-related morphological changes. Our results demonstrate altered cilia motility in systemic and reproductive organs, with such morphological changes of the infundibulum likely impairing function, including oocyte pickup.
• Anti-Ku antibody-related scleroderma-polymyositis overlap syndrome associated with thrombocytopaenia.

  T Horino, H Nishikawa, S Inotani, T Matsumoto, O Ichii, Y Terada

  QJM : monthly journal of the Association of Physicians 113 (5) 349 - 350 2020/05/01 [Refereed][Not invited]
  
• Expression of Peroxisome Proliferator-activated Receptor-γ in the Kidneys of Cats with Chronic Kidney Disease.

  A Yabuki, Y Uehara, O Ichii, C Yoshida, O Yamato

  Journal of comparative pathology 176 81 - 85 2020/04 [Refereed][Not invited]
   

  Peroxisome proliferator-activated receptor (PPAR)-γ plays an important role in various cellular functions and its activation exerts protective effects in kidney diseases. In the present study, chronic kidney disease in cats was examined, and changes in renal expression of PPARγ were observed by use of immunohistochemistry. In normal kidneys, nuclei of the superficial cortical tubules, medullary tubules and glomerular cells expressed PPARγ. The vascular walls (tunica media) also showed positive expression. In diseased kidneys, the expression of PPARγ varied between the cases. Some cases showed strong expression, while others had weak expression. PPARγ expression in the nuclei of infiltrating mononuclear cells was also detected in over half of the cases. Although there was no significant relationship between the expression of renal PPARγ and the severity of kidney disease, the fact that there were many cases where the expression of renal PPARγ was reduced was an important finding, and might be one of the possible mechanisms underlying feline chronic kidney diseases.
• Morphological and molecular identification of cyathostomine gastrointestinal nematodes of Murshidia and Quilonia species from Asian elephants in Myanmar.

  Hla Myet Chel, Takashi Iwaki, Myint Myint Hmoon, Yu Nandi Thaw, Nyein Chan Soe, Shwe Yee Win, Saw Bawm, Lat Lat Htun, Mar Mar Win, Zaw Min Oo, Md Abdul Masum, Osamu Ichii, Ryo Nakao, Nariaki Nonaka, Ken Katakura

  International journal for parasitology. Parasites and wildlife 11 294 - 301 2020/04 [Refereed][Not invited]
   

  Gastrointestinal nematode parasites have long been recognized in Asian elephants. The most common parasites belong to the subfamily Cyathostominae of the family Strongylidae, which are small to medium-sized with a cylindrical buccal capsule surrounded by coronal leaflets. Diagnostic keys of such parasites are provided from old illustrations in the form of line drawings. However, there very few photomicrographs and no genetic information of these parasites exist. In the present study we obtained adult worm specimens from faeces of Asian elephants after anthelmintic treatment in two elephant camps in Myanmar. Here, we provided photomicrographs for five cyathostomine parasites, Murshidia falcifera, Murshidia indica, Murshidia neveulemairei, Quilonia renniei, and Quilonia travancra almost 100 years after their original drawings. In addition, we determined the mitochondrial cytochrome c oxidase subunit I (COI) gene sequences of these species. Phylogenetic analysis of the COI genes of Murshidia and Quilonia species from Asian and African elephants revealed parasite speciation in each elephant host. The present study also indicated that several Murshidia and Quilonia species were widely distributed in Asian elephants in Myanmar, providing new insight into control strategies and evolution of cyathostomine gastrointestinal parasites in elephants.
• Macromolecular creatine kinase Type 1 in a patient with anti-aminoacyl-tRNA synthetase autoantibody-related dermatomyositis.

  T Horino, S Inotani, T Matsumoto, O Ichii

  QJM : monthly journal of the Association of Physicians 113 (3) 201 - 202 2020/03/01 [Refereed][Not invited]
  
• Autoimmune polyglandular syndrome type 3 variant in rheumatoid arthritis.

  Taro Horino, Masami Ogasawara, Osamu Ichii, Yoshio Terada

  Romanian journal of internal medicine = Revue roumaine de medecine interne 58 (1) 40 - 43 2020/03/01 [Refereed][Not invited]
   

  INTRODUCTION: Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant. CASE REPORT: A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves' disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy. CONCLUSION: In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.
• Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Spondyloarthropathy-Related Aortitis.

  Taro Horino, Satoshi Inotani, Tatsuki Matsumoto, Osamu Ichii

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2020/02/05 [Refereed][Not invited]
  
• Immune-associated renal disease found in caspase 3-deficient mice.

  Takashi Suzuki, Osamu Ichii, Teppei Nakamura, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Cell and tissue research 379 (2) 323 - 335 0302-766X 2020/02 [Refereed][Not invited]
   

  Caspase (CASP) 3 is known as a representative effector CASP of apoptosis and recently as a mediator in inflammatory cell death called pyroptosis. Interestingly, homozygotes of Casp3 knockout (KO) mice with 129-background show complete embryonic lethality; however, some of those with C57BL/6 (B6)-background (B6.129S1-Casp3tm1Flv/J) survived at a lower rate (KO, 11%; WT, 22%), developing immune abnormality-associated renal phenotypes. Homozygotes of Casp3 KO mice with B6-background that survived for 8-12 months showed abnormality in the kidney and spleen but not in other organs. Briefly, these Casp3 KO kidneys showed proliferative glomerular lesions characterized by increased cells, matrices, immune complex depositions containing IgA and complement 3 in the mesangial area, podocyte injuries and inflammatory cell infiltrations in the tubulointerstitium. However, severe membranous lesion or renal dysfunction was not observed. Increased expression of inflammation-associated gene sets and inflammatory Casps, including Casp12, was observed in these Casp3 KO kidneys. Moreover, these Casp3 KO mice showed mild splenomegaly compared with WT mice. Thus, the long-surviving Casp3 KO mice with B6-background developed renal lesions with altered immune conditions. CASP3 deficiency and aging factors could affect this phenotype by altering the function and/or development of each cell in the kidney and immune organs.
• A Case of Behçet Disease Concurrent With Giant Saccular Abdominal Aortic Aneurysm.

  Taro Horino, Osamu Ichii

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2020/01/15 [Refereed][Not invited]
  
• Age-related glomerular lesions with albuminuria in male cotton rats.

  Osamu Ichii, Teppei Nakamura, Takao Irie, Yuki Otani, Marina Hosotani, Md Abdul Masum, Rashedul Md Islam, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Histochemistry and cell biology 153 (1) 27 - 36 2020/01 [Refereed][Not invited]
   

  The increased prevalence of aging-related chronic kidney disease (CKD) among humans is a problem worldwide. Aged cotton rats (Sigmodon hispidus) are considered novel model animals for studying CKD, especially as the females develop severe tubulointerstitial lesions with anemia. To investigate the renal pathologic features in aged male cotton rats and their characteristic glomerular injuries, the animals were divided into young, adult, old-aged, and advanced-aged groups (1-4, 5-8, 9-12, and 13-17 months, respectively) and pathologically analyzed. Anemia and renal dysfunction, as indicated by hematologic and serologic parameters, were significantly milder in the advanced-aged males than in the old-aged females. The males had increased urinary albumin-to-creatinine ratios from the old-age period, with the advanced-aged males having significantly higher levels than those in the old-aged females and young males. The old-aged females did not show clear glomerular injuries, whereas the advanced-aged males showed membranous lesions characterized by irregular and thickened glomerular basement membranes (GBMs). Characteristically, several large-sized projections from the GBM toward the podocytes were observed by microscopy, and podocytes covering these projections effaced their foot processes. The advanced-aged males showed aging-related IgG immune-complex depositions in the paramesangial regions and along the GBM. Furthermore, the positive reaction for podocin (a podocyte molecule) was granulated along the GBM. Thus, we clarified the albuminuria associated with altered glomerular structures in advanced-aged cotton rats, and that these phenotypes were closely associated with aging. These data help to clarify the aging-related pathogenesis of glomerular injury.
• Intestinal Spirochetosis Caused by Brachyspira pilosicoli in a Systemic Lupus Erythematosus Patient.

  Tomohiro Eguchi, Kosuke Inoue, Taro Horino, Tatsuki Matsumoto, Saya Kamioka, Yoshie Nishida, Miyuki Morimoto, Norihito Morimoto, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 25 (8) e142-e145  2019/12 [Refereed][Not invited]
  
• Molecular characterization of three Sarcocystis spp. from wild sika deer (Cervus nippon yesoensis) in Hokkaido, Japan.

  Takao Irie, Osamu Ichii, Teppei Nakamura, Tetsuya Ikeda, Takuya Ito, Akiko Yamazaki, Shinji Takai, Kinpei Yagi

  Veterinary parasitology, regional studies and reports 18 100327 - 100327 2019/12 [Refereed][Not invited]
   

  Diaphragm samples from 65 hunted sika deer (Cervus nippon yesoensis) from Hokkaido, Japan were examined for the presence of sarcocysts based on histological sections. Morphologically, the detected sarcocysts grouped into three types: (Type 1) 108.0-305.0 μm in width, thick-walled (4.3-7.0 μm) with tombstone-like protrusions; (Type 2) 25.0-69.5 μm in width, thick-walled (3.8-8.0 μm) with finger-like protrusions; and (Type 3) 22.5-55.0 μm in width, thin-walled (under 1 μm) with no visible protrusions under light microscopy. All samples contained at least one sarcocyst type, and multiparasitism was apparent in 58 samples. Morphologically, Type 1 sarcocysts were found in 19 (29.2%) samples, Type 2 in 62 (95.4%) samples, and Type 3 in 60 (92.3%) samples. The sarcocysts were collected using laser microdissection, the DNA extracted from them was PCR-amplified, and their 18S ribosomal RNA and cytochrome c oxidase subunit 1 genes were sequenced. Phylogenetic analysis showed that, for both genes, each morphological sarcocyst type (Types 1, 2, and 3) aligned most closely with S. silva/S. truncata, S. tarandi/S. elongata, and S. pilosa, respectively. Based on the sequence identities between taxa and the molecular information for sarcocysts in C. nippon centralis, the sarcocyst types were presumed to be S. truncata-like (Type 1), S. tarandi-like (Type 2), and S. pilosa (Type 3). The phylogenetic analyses based on the present comprehensive molecular characterization of three Sarcocystis spp. from C. nippon yesoensis in Hokkaido suggest that canids (e.g., wild foxes) may be the definitive hosts for S. pilosa, and felids (or unknown species) the definitive hosts for the other two species.
• Tissue distribution and characterization of feline cytochrome P450 genes related to polychlorinated biphenyl exposure.

  Kraisiri Khidkhan, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M M Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Wageh Sobhy Darwish, Mitsuyoshi Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 226 108613 - 108613 2019/12 [Refereed][Not invited]
   

  Cats have been known to be extremely sensitive to chemical exposures. To understand these model species' sensitivity to chemicals and their toxicities, the expression profiles of xenobiotic-metabolizing enzymes should be studied. Unfortunately, the characterization of cytochrome P450 (CYP), the dominant enzyme in phase I metabolism, in cats has not extensively been studied. Polychlorinated biphenyls (PCBs) are known as CYP inducers in animals, but the information regarding the PCB-induced CYP expression in cats is limited. Therefore, in the present study, we aimed to elucidate the mRNA expression of the CYP1-CYP3 families in the cat tissues and to investigate the CYP mRNA expression related to PCB exposure. In cats, the greatest abundance of CYP1-CYP3 (CYP1A2, CYP2A13, CYP2C41, CYP2D6, CYP2E1, CYP2E2, CYP2F2, CYP2F5, CYP2J2, CYP2U1, and CYP3A132) was expressed in the liver, but some extrahepatic isozymes were found in the kidney (CYP1A1), heart (CYP1B1), lung (CYP2B11 and CYP2S1) and small intestine (CYP3A131). In cats, CYP1A1, CYP1A2 and CYP1B1 were significantly upregulated in the liver as well as in several tissues exposed to PCBs, indicating that these CYPs were distinctly induced by PCBs. The strong correlations between 3,3',4,4'-tetrachlorobiphenyl (CB77) and CYP1A1 and CYP1B1 mRNA expressions were noted, demonstrating that CB77 could be a potent CYP1 inducer. In addition, these CYP isoforms could play an essential role in the PCBs biotransformation, particularly 3-4 Cl-PCBs, because a high hydroxylated metabolite level of 3-4 Cl-OH-PCBs was observed in the liver.
• Distal Phalanx Osteolysis and Subcutaneous Calcinosis in CREST Syndrome.

  Taro Horino, Osamu Ichii

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2019/11/22 [Refereed][Not invited]
  
• Slc:Hartley guinea pigs frequently possess duplication of the caudal vena cava.

  Teppei Nakamura, Miyuki Norimura, Kanako Sumi, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon, Osamu Tatsumi, Hideki Hattori, Tomoji Yoshiyasu, Ken-Ichi Nagasaki

  Experimental animals 68 (4) 465 - 470 1341-1357 2019/11/06 [Refereed][Not invited]
   

  The formation of the caudal vena cava is a complex process involving development, regression, and anastomosis. In mammals, the normal caudal vena cava runs to the right side of the abdominal aorta, while duplication of the caudal vena cava has been identified as a congenital abnormality in both companion animals and humans. The present study demonstrates that Slc:Hartley guinea pigs frequently possess asymptomatic duplicated caudal vena cava. The prevalence was 30% and 24% for males and females, respectively, with no sex-related differences. In accordance with Saad et al. (2012)'s criteria, duplicated caudal vena cava were classified into two distinct variations. The dominant variation was a complete duplication without iliac anastomosis where the left caudal vena cava continued from the left common iliac vein and joined the left renal vein; the left renal vein ran to the right to join the right caudal vena cava. The alternative variation was an incomplete duplication where the left caudal vena cava joined the right infrarenal caudal vena cava at a more cranial point than in normal cases; the renal segment was unchanged. Iliac anastomosis was not found in any cases. Duplicated caudal vena cava neither affected the body weight nor the kidney weight. In conclusion, Slc:Hartley guinea pigs frequently possess asymptomatic duplicated caudal vena cava in the absence of iliac anastomosis and appear to be a novel and useful animal model for duplicated caudal vena cava in animals and humans.
• Reactive Arthritis Caused by Rothia mucilaginosa in an Elderly Diabetic Patient.

  Taro Horino, Satoshi Inotani, Tatsuki Matsumoto, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2019/10/23 [Refereed][Not invited]
  
• Effects of PCB exposure on serum thyroid hormone levels in dogs and cats.

  Kohki Takaguchi, Hiroyuki Nishikawa, Hazuki Mizukawa, Rumi Tanoue, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shouta M M Nakayama, Yoshinori Ikenaka, Tatsuya Kunisue, Mayumi Ishizuka, Shinsuke Tanabe, Hisato Iwata, Kei Nomiyama

  The Science of the total environment 688 1172 - 1183 2019/10/20 [Refereed][Not invited]
   

  Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.
• Renal Infiltration of Macrophages in Canine and Feline Chronic Kidney Disease.

  Y Ohara, A Yabuki, R Nakamura, O Ichii, H Mizukawa, N Yokoyama, O Yamato

  Journal of comparative pathology 170 53 - 59 0021-9975 2019/07 [Refereed][Not invited]
   

  During the progression of chronic kidney disease (CKD), macrophage infiltration is a crucial event leading to tubulointerstitial fibrosis. In the present study, macrophages infiltrating renal tissue in dogs and cats with CKD were analysed immunohistochemically. Iba-1 was used as a pan-macrophage marker, CD204 was used as a marker of M2 macrophages and tumour necrosis factor (TNF)-α was used as a marker of M1 macrophages. Signals for Iba1 and CD204 were observed in the interstitium of all tested kidney samples. In dogs, the signals were diffusely scattered. In cats, both diffuse and focal signals were observed. Cells that were positive for Iba1 and CD204 were also observed in the tubular lumina in cats. Co-expression of Iba1 and CD204 was also observed in the infiltrating cells by immunofluorescence labelling, and these cells were negative for TNF-α. By quantitative analysis, the indices for Iba1- and CD204-positive cells were significantly correlated with the concentrations of plasma creatinine and/or urea and the extent of interstitial fibrosis in both dogs and cats. These results demonstrated that renal infiltration of M2 macrophages plays an important role in the progression of CKD in dogs and cats. The distribution pattern of the kidney-infiltrating macrophages was unique in cats and may be associated with a cat-specific renal fibrotic process.
• Histopathological features of the proper gastric glands in FVB/N-background mice carrying constitutively-active aryl-hydrocarbon receptor.

  Ai Dantsuka, Osamu Ichii, Annika Hanberg, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Teppei Nakamura, Yasuhiro Kon

  BMC gastroenterology 19 (1) 102 - 102 1471-230X 2019/06/21 [Refereed][Not invited]
   

  BACKGROUND: Aryl-hydrocarbon receptor (AhR) is a multiple ligand-activated transcription factor that has important roles in xenobiotic, physiological, or pathological functions. Transgenic mice systemically expressing constitutively-active AhR (CA-AhR) have been created to mimic activated AhR signaling in vivo. However, their detailed histopathological features are unclear. In the present study, we generated CA-AhR-expressing FVB/N mice (FVB-CA-AhR mice) and clarified their phenotypes in detail. METHODS: Male and female FVB-CA-AhR and wild-type mice were histopathologically examined from 6 to 33 weeks of age. RESULTS: Among the systemic organs, only the stomachs in FVB-CA-AhR mice showed pathological changes including cystic structures beneath the serosa; in addition, stomach weights increased with age. Histopathologically, cystic structures and alcian blue-positive metaplasia were observed in the mucosa of the proper gastric glands, and these two histometric parameters were positively correlated. Furthermore, proliferating cells shifted from the isthmus to the base of the glands, and parietal cells decreased. Age-related histopathological changes were clearer in females than in males. Importantly, in FVB-CA-AhR mice, intramucosal cysts developed as extramucosal cysts beneath the serosa, penetrating the lamina muscularis mucosae and the muscularis propria. Their incidence reached 100% in 28-week-old male mice and 33-week-old female mice. Extramucosal cysts contained alcian blue-, Griffonia simplicifolia lectin II-, or trefoil factor 2-positive cells, suggesting a stomach origin for the cysts and spasmolytic polypeptide-expressing metaplasia-like lesions. CONCLUSIONS: Disease onset occurred earlier in FVB-CA-AhR mice than previously reported in C57BL/6-derived CA-AhR mice. Importantly, the histopathological features were partly similar with gastritis cystica profunda in humans and animals. Excessive activation of AhR signaling aggravated abnormalities in the gastric mucosa and were affected by both genetic- and sex-related factors.
• Cotton Wool Sign in Paget Disease of Bone.

  Taro Horino, Osamu Ichii, Yoshio Terada

  Internal medicine (Tokyo, Japan) 58 (12) 1809 - 1810 2019/06/15 [Refereed][Not invited]
  
• Overlapping Syndrome of Systemic Scleroderma and Cryoglobulinemic Vasculitis.

  Taro Horino, Kazu Hamada-Ode, Osamu Ichii, Yoshio Terada

  The American journal of medicine 132 (6) e589-e590  2019/06 [Refereed][Not invited]
  
• A Rare Presentation of Hypermagnesemia Associated with Acute Kidney Injury due to Hypercalcemia.

  Taro Horino, Osamu Ichii, Yoshio Terada

  Internal medicine (Tokyo, Japan) 58 (8) 1123 - 1126 2019/04/15 [Refereed][Not invited]
   

  A 79-year-old Japanese woman presented with consciousness disturbance, hypercalcemia, and hypermagnesemia. She had rheumatoid arthritis and osteoporosis. Three months before admission, she was treated with oral calcitriol for osteoporosis. Two months before admission, she was treated with magnesium oxide for constipation. One month before admission, she underwent articular femoral bone replacement. Two weeks postoperatively, consciousness disturbance and elevated serum calcium levels were observed, and she was transferred to our hospital. On admission, her laboratory data showed elevated serum magnesium and creatinine levels. This is a rare case of coexistent hypercalcemia and hypermagnesemia associated with consciousness disturbance and acute kidney injury.
• Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) caused by levofloxacin in a patient with systemic scleroderma, rheumatoid arthritis, and Sjogren syndrome.

  Tatsuki Matsumoto, Taro Horino, Satoshi Inotani, Osamu Ichii, Yoshio Terada

  Contact dermatitis 80 (4) 253 - 254 2019/04 [Refereed][Not invited]
  
• Spondyloarthropathy associated with glycogen storage disease type V mimicking polymyositis.

  T Horino, E Amano, T Furushima, O Ichii, Y Terada

  QJM : monthly journal of the Association of Physicians 112 (4) 281 - 282 2019/04/01 [Refereed][Not invited]
  
• IgA-Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits.

  Taro Horino, Osamu Ichii, Yoshio Terada

  The American journal of medicine 132 (4) e542-e545  2019/04 [Refereed][Not invited]
  
• Feature Article: Altered morpho-functional features of bones in autoimmune disease-prone BXSB/MpJ- Yaa mice.

  Takashi Namba, Osamu Ichii, Teppei Nakamura, Md Abdul Masum, Yuki Otani, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Experimental biology and medicine (Maywood, N.J.) 244 (5) 333 - 343 2019/04 [Refereed][Not invited]
   

  IMPACT STATEMENT: Bone disease, such as osteoporosis and rheumatoid arthritis, increases because of the progression of an aging society. Autoimmune disease are important and predisposing factors for the pathogenesis of the bone disease; however, the pathological mechanism is unclear. We have demonstrated that systemic autoimmune disease in BXSB/MpJ- Yaa is closely associated with the morpho-functional abnormalities of bones including bone marrow and has complicated pathology. The abnormalities are characterized by altered regulations of serum calcium, anemia tendency, and hematopoiesis with increased WBCs and decreased PLs, short length and low mass of long bones, imbalance in the populations of osteoclasts and osteoblasts, and increased expression of candidate genes for causing and/or exacerbating their phenotypes. Therefore, BXSB/MpJ- Yaa serves as a model to elucidate bone phenotypes in systemic autoimmune disease that would be affected by the factors in the bone as well as the other immune and/or mineral metabolism organs both in human and experimental medicine.
• MRL/MpJ mice produce more oocytes and exhibit impaired fertilisation and accelerated luteinisation after superovulation treatment.

  Marina Hosotani, Osamu Ichii, Teppei Nakamura, Md Abdul Masum, Yuki Otani, Saori Otsuka-Kanazawa, Yaser H A Elewa, Yasuhiro Kon

  Reproduction, fertility, and development 31 (4) 760 - 773 1031-3613 2019/04 [Refereed][Not invited]
   

  MRL/MpJ mice exhibit distinct phenotypes in several biological processes, including wound healing. Herein we report two unique phenotypes in the female reproductive system of MRL/MpJ mice that affect ovulation and luteinisation. We found that superovulation treatment resulted in the production of significantly more oocytes in MRL/MpJ than C57BL/6 mice (71.0±13.4 vs 26.8±2.8 respectively). However, no exon mutations were detected in genes coding for female reproductive hormones or their receptors in MRL/MpJ mice. In addition, the fertilisation rate was lower for ovulated oocytes from MRL/MpJ than C57BL/6 mice, with most of the fertilised oocytes showing abnormal morphology, characterised by deformation and cytolysis. Histological tracing of luteinisation showed that MRL/MpJ mice formed corpora lutea within 36h after ovulation, whereas C57BL/6 mice were still at the corpora haemorrhagica formation stage after 36h. The balance between the expression of matrix metalloproteinases and their tissue inhibitors shifted towards the former earlier after ovulation in MRL/MpJ than C57BL/6 mice. This result indicates a possible link between accelerated extracellular matrix remodelling in the ovulated or ruptured follicles and luteinisation in MRL/MpJ mice. Together, these findings reveal novel phenotypes in MRL/MpJ mice that provide novel insights into reproductive biology.
• The intratumor heterogeneity of TP53 gene mutations in canine histiocytic sarcoma.

  Hajime Asada, Osamu Ichii, Hirotaka Tomiyasu, Kazuyuki Uchida, James K Chambers, Yuko Goto-Koshino, Koichi Ohno, Yasuhiro Kon, Hajime Tsujimoto

  The Journal of veterinary medical science 81 (3) 353 - 356 0916-7250 2019/03/14 [Refereed][Not invited]
   

  The mutations of TP53 gene are frequently observed in canine histiocytic sarcoma (HS). The objective of this study was to examine the distribution of tumor cells with TP53 gene mutations. Tumor tissues were divided into three or four regions and TP53 gene mutations were examined. TP53 gene mutations were detected only in parts of the HS tissues from six of the eight dogs, and the frequency of the mutant allele varied (0-65%) among the tumor regions. This study suggests that canine HS can exhibit intratumor heterogeneity. Further studies are needed to examine the clinical significance of the intratumor heterogeneity of TP53 gene mutations.
• Monoclonal Gammopathy of Undetermined Significance in a Patient With Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) Syndrome: Coincidence or Association?

  Taro Horino, Masami Ogasawara, Tatsuki Matsumoto, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2019/03/12 [Refereed][Not invited]
  
• Is recurrent Kikuchi-Fujimoto disease a precursor to systemic lupus erythematosus?

  Taro Horino, Osamu Ichii, Yoshio Terada

  Romanian journal of internal medicine = Revue roumaine de medecine interne 57 (1) 72 - 77 2019/03/01 [Refereed][Not invited]
   

  Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign, self-limiting disease characterized by cervical lymphadenopathy and fever. Since KFD was first reported in 1972, the validity of this clinical entity has been controversial and its aetiology remains unknown. Herein, we report a case of a patient with KFD, which was believed to be associated with systemic lupus erythematosus.
• Response to Makino: 'Hereditary spherocytosis presenting with branch retinal artery occlusion'.

  T Horino, O Ichii, T Asagiri, T Eguchi, Y Terada

  QJM : monthly journal of the Association of Physicians 112 (3) 239 - 240 2019/03/01 [Refereed][Not invited]
  
• Food Yellow4 reprotoxicity in relation to localization of DMC1 and apoptosis in rat testes: Roles of royal jelly and cod liver oil.

  Yaser H A Elewa, Amany Abdel-Rahman Mohamed, Azza A A Galal, Nesma I El-Naseery, Osamu Ichii, Yasuhiro Kon

  Ecotoxicology and environmental safety 169 696 - 706 2019/03 [Refereed][Not invited]
   

  Food Yellow 4 (FY4) is a lemon-yellow-colored synthetic organic azo dye, which is used widely for imparting pleasant and attractive appearance to foods and cosmetics. The present study aimed at evaluating the possible mechanism underlying the FY4-induced reprotoxicity in rats, and the potential supportive role of royal jelly (RJ) or cod liver oil (CLO), which is a natural remedy with several pharmacological benefits, against induced toxicity. Forty-eight male rats were divided into different groups-the control group, the CLO group (0.4 mL/kg), the RJ group (300 mg/kg), the FY4 group (500 mg/kg b.w.), and the co-treated groups (FY4 + CLO or FY4 + RJ). Semen analysis, serum hormones, and enzyme activities were estimated. Immunohistochemical staining was performed using anti-PCNA, anti-Sox 9, anti-STRA8, anti-DMC1, and anti-ssDNA antibody. The FY4 group exhibited a significant decrease in sperm concentration and motility percentage (%) and a substantial reduction in the TES and LH levels. Testicular LDH, ACP, and SDH were observed to be inhibited. Furthermore, co-localization of DMC1 and ssDNA, which reflected apoptotic induction in the leptotene and zygotene spermatocytes, respectively, was observed to have markedly elevated in the FY4 treated rats, with fewer PCNA-positive and SOX9-positive cells and higher ssDNA-positive cells in the seminiferous epithelium in comparison to the control groups. Interestingly, co-treatment with CLO or RJ exhibited healthy sperms and restored their features, activated the enzyme production, and raised the levels of sexual hormones. In addition, both RJ and CLO restored the features of the testicular tissue as observed under a light microscope, and limited the apoptosis as observed through antibody staining. Collectively, the results of the present study revealed that the co-administration of RJ or CLO with FY4 improved the biochemical, hormonal, and structural aspects of the testicular tissue in rats. Therefore, CLO and RJ may be considered promising agents that would be able to improve the testicular structure and function in the FY4-exposed individuals.
• Reactive Arthritis Caused by Haemophilus parainfluenzae in a Diabetic Patient.

  Tomohiro Eguchi, Taro Horino, Eri Amano, Osamu Ichii, Yoshio Terada

  The American journal of medicine 132 (3) e519-e520  2019/03 [Refereed][Not invited]
  
• Induced expression of Toll-like receptor 9 in peritubular capillary endothelium correlates with the progression of tubulointerstitial lesions in autoimmune disease-prone mice.

  M A Masum, O Ichii, Y H A ELewa, Y Kon

  Lupus 28 (3) 324 - 333 2019/03 [Refereed][Not invited]
   

  BACKGROUND: Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood-urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of peritubular capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice. METHODS: Lupus-prone BXSB/MpJ-Yaa (Yaa) and BXSB/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis. RESULTS: Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24 wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24 wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta ( Il1b), Il6, interferon gamma ( Ifng), and tumor necrosis factor alpha ( Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24 wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24 wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules ( P < 0.05 and 0.01). CONCLUSION: Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.
• Cotton rat (Sigmodon hispidus) develops metabolic disorders associated with visceral adipose inflammation and fatty pancreas without obesity.

  Teppei Nakamura, Osamu Ichii, Takao Irie, Hirokazu Kouguchi, Kozue Sotozaki, Masataka Chihara, Yuji Sunden, Ken-Ichi Nagasaki, Osamu Tatsumi, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Cell and tissue research 375 (2) 483 - 492 0302-766X 2019/02 [Refereed][Not invited]
   

  Obesity induces metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular diseases and has become a global health concern. Recent studies imply that fat accumulation in nonadipose tissue correlates with metabolic disorders. However, there are no suitable animal models to evaluate this phenomenon. This study investigated the characteristics of metabolic disorders found in cotton rat (Sigmodon hispidus). Blood biochemical examinations revealed that cotton rats, predominantly males, developed hyperinsulinemia, hyperglycemia, and dyslipidemia when fed a normal diet. The islets increased in size through β-cell hyperplasia, which was associated with serum insulin level in both sexes, strongly indicating insulin resistance. In male cotton rats, oxidative stress was observed in β cells, and macrophage infiltration into the visceral white adipose tissue was reported, both of which were associated with serum insulin level without visceral obesity. In contrast, female cotton rats developed hyperinsulinemia without histopathological changes that were reported in males. Adipocytes were found to be accumulated in the pancreas but not in the liver of both sexes during aging. Pancreatic fat accumulation was associated with the serum insulin level only in females. Taken together, cotton rats developed metabolic disorders associated with visceral fat inflammation in the absence of obesity. In addition, pancreatic ectopic fat may also be related to the early stages of these conditions. Thus, the cotton rat may serve as a novel and useful model for metabolic disorders characterized by visceral adipose inflammation and ectopic fat accumulation in the pancreas without obesity.
• Relapsing Polychondritis Associated With Psoriasis Vulgaris.

  Taro Horino, Osamu Ichii, Tatsuki Matsumoto, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2019/01/04 [Refereed][Not invited]
  
• Whole immunofluorescence staining of podocytes in fabry disease.

  Taro Horino, Toru Kubo, Osamu Ichii, Tatsuki Matsumoto, Kazu Hamada-Ode, Yoshio Terada

  Nephrology (Carlton, Vic.) 24 (1) 135 - 135 2019/01 [Refereed][Not invited]
  
• Slc:Wistar/ST rats develop unilateral thyroid dysgenesis: A novel animal model of thyroid hemiagenesis.

  Teppei Nakamura, Osamu Ichii, Yuji Sunden, Yaser Hosny Ali Elewa, Tomoji Yoshiyasu, Hideki Hattori, Osamu Tatsumi, Yasuhiro Kon, Ken-Ichi Nagasaki

  PloS one 14 (8) e0221939  2019 [Refereed][Not invited]
   

  Developmental anomalies of the thyroid gland lead to congenital malformations such as thyroglossal duct cysts and thyroid dysgenesis. However, the pathogenesis of thyroid dysgenesis remains unclear due to the lack of suitable animal models. This study demonstrated that Slc:Wistar/ST rats frequently developed unilateral thyroid dysgenesis, including hemiagenesis, characterized by the absence of one lobe. In Wistar/ST rats, each thyroid lobe was frequently different in size, and approximately 27% and 20% of the rats presented with hemihypoplasia and hemiagenesis of the thyroid gland, respectively. Dysgenesis was predominant on the left side in both sexes, without sex differences. At a young age, thyroid hemiagenesis did not alter body weight. In rats of both sexes with thyroid hemiagenesis, plasma total triiodothyronine and total triiodothyronine levels remained unchanged while plasma thyroid-stimulating hormone levels were significantly elevated in young rats. The remaining thyroid lobes increased in weight, but the follicular epithelial cells appeared normal in terms of their height and proliferating activities. On the side of thyroid dysgenesis, the parathyroid glands were normally localized and were situated at the same location as the contralateral glands. The ultimobranchial body remnants were localized at the level of the thyroid gland along with the cranial thyroid artery and vein, forming cell clusters or cystic structures and containing calcitonin-positive C-cells. In conclusion, Wistar/ST rats developed unilateral thyroid dysgenesis and may be novel and useful animal models for thyroid hemiagenesis in humans and for morphogenesis of pharyngeal pouch-derived organs.
• Corrigendum: Urinary Exosome-Derived microRNAs Reflecting the Changes in Renal Function in Cats.

  Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Frontiers in veterinary science 6 2 - 2 2019 [Refereed][Not invited]
   

  [This corrects the article DOI: 10.3389/fvets.2018.00289.].
• iBTA-induced bovine Biosheet for repair of abdominal wall defects in a beagle model: proof of concept.

  Y Nakayama, N Oshima, E Tatsumi, O Ichii, T Nishimura

  Hernia : the journal of hernias and abdominal wall surgery 22 (6) 1033 - 1039 1265-4906 2018/12 [Refereed][Not invited]
   

  INTRODUCTION: We evaluated the usefulness of xeno-Biosheets, an in-body tissue architecture-induced bovine collagenous sheet, as repair materials for abdominal wall defects in a beagle model. MATERIALS AND METHODS: Biosheets were prepared by embedding cylindrical molds into subcutaneous pouches of three Holstein cows for 2-3 months and stored in 70% ethanol. The Biosheets were 0.5 mm thick, cut into 2 cm × 2 cm, and implanted to replace defects of the same size in the abdominal wall of nine beagles. The abdominal wall and Biosheets were harvested and subjected to histological evaluation at 1, 3, and 5 months after implantation (n = 3 each). RESULTS: The Biosheet and bovine pericardiac patch (control) were not stressed during the suture operation and did not split, and patches were easily implanted on defective wounds. After implantation, the patch did not fall off and was not perforated, and healing was observed nacroscopically in all cases. During the first month of implantation, accumulation of inflammatory cells was observed along with decomposition around the Biosheet. Decomposition was almost complete after 3 months, and the Biosheet was replaced by autologous collagenous connective tissue without rejection. After 5 months, the abdominal wall muscle elongated from the periphery of the newly formed collagen layer and the peritoneum was formed on the peritoneal cavity surface. Regeneration of almost all layers of the abdominal wall was observed. However, almost all pericardium patches were remained even at 5 months with inflammation. CONCLUSION: Bovine Biosheets requiring no special post-treatment can be useful as off-the-shelf materials for abdominal wall repair.
• Hereditary spherocytosis presenting with branch retinal artery occlusion.

  T Horino, O Ichii, T Asagiri, T Eguchi, Y Terada

  QJM : monthly journal of the Association of Physicians 111 (12) 899 - 900 1460-2725 2018/12/01 [Refereed][Not invited]
  
• Overexpression of toll-like receptor 9 correlates with podocyte injury in a murine model of autoimmune membranoproliferative glomerulonephritis.

  Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yuki Otani, Marina Hosotani, Yasuhiro Kon

  Autoimmunity 51 (8) 386 - 398 0891-6934 2018/12 [Refereed][Not invited]
   

  Toll-like receptors (Tlrs) are sensors of danger signals which promote the activation of immune cells and intrinsic renal cells. Podocytes, the intrinsic cells of glomerulus, are continuously exposed to various plasma solutes and danger signals due to their unique location in the glomerulus. Herein, we show that Tlr9 is overexpressed in podocytes and the mechanisms which cause its injury and development of membranoproliferative glomerulonephritis (MPGN) in model BXSB/MpJ-Yaa (Yaa) mice. Yaa mice developed typical lesions of MPGN and showed strong expression of Tlr9 mRNA throughout the glomerulus particularly toward the periphery of the glomerulus. However, BXSB/MpJ (BXSB) mice showed no lesion for MPGN but a very weak expression of Tlr9 mRNA. Relative mRNA expression of Tlr9 and its downstream cytokines, including interleukin 1 beta (Il1b), Il6, interferon gamma (Ifng) and tumour necrosis factor alpha (Tnfa) was markedly increased in glomeruli isolated from Yaa mice. Tlr9 protein expression was almost absent in BXSB mice but intense expression was found in Yaa mice. Podocyte protein expression was normal in BXSB mice but decreased in Yaa mice and colocalized with Tlr9 protein. Furthermore, electron microscopy examination revealed podocyte injury and electron-dense materials in thickened glomerular basement membrane of Yaa mice. Glomerular Tlr9 mRNA expression was significantly correlated with anti-dsDNA antibody, proteinuria, renal function indices (sBUN and sCr), glomerular histopathology indices, downstream factors of Tlr family (Ilb and Tnfa), podocyte injury parameters (p < .05 and p < .01). In conclusion, overexpression of TLR9 correlates with podocyte injury and development of MPGN.
• Analysis for genetic loci controlling protoscolex development in the Echinococcus multilocularis infection using congenic mice.

  Md Atiqul Islam, Daisuke Torigoe, Yayoi Kameda, Takao Irie, Hirokazu Kouguchi, Ryo Nakao, Md Abdul Masum, Osamu Ichii, Yasuhiro Kon, Hassan T Tag-El-Din-Hassan, Masami Morimatsu, Kinpei Yagi, Takashi Agui

  Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 65 65 - 71 1567-1348 2018/11 [Refereed][Not invited]
   

  The resistance/susceptibility to Echinococcus multilocularis infection in mice is genetically controlled. However, genetic factors responsible for these differences remain unknown. Our previous study in genetic linkage analysis has revealed that there is a significant quantitative trait locus (QTL) for the establishment of cyst (Emcys1), and a highly significant QTL for the development of protoscolex of E. multilocularis larvae (Empsc1), on mouse chromosomes 6 and 1, respectively. The current study aimed to confirm these QTLs and narrow down the critical genetic region that controls resistance/susceptibility to E. multilocularis infection by establishing congenic and subcongenic lines from C57BL/6 (B6) and DBA/2 (D2) mice. For protoscolex development phenotype, two congenic lines, B6.D2-Empsc1 and D2.B6-Empsc1 were developed, where responsible QTL, Empsc1 was introgressed from D2 into B6 background and vice versa. For cyst establishment phenotype, two congenic lines, B6.D2-Emcys1 and D2.B6-Emcys1 were developed, where responsible QTL, Emcys1 was introgressed from D2 into B6 background and vice versa. Because there was no significant difference in cyst establishment between B6.D2-Emcys1 and D2.B6-Emcys1 mice after challenge with E. multilocularis, it is suggested that the Emcys1 does not solely control the cyst establishment in mouse liver. However, infection experiments with B6.D2-Empsc1 and D2.B6-Empsc1 mice showed a significant difference in protoscolex development in the cyst. It confirms that the Empsc1 controls phenotype of the protoscolex development in the cyst. Subsequently, two subcongenic lines, B6.D2-Empsc1.1 and B6.D2-Empsc1.2 from B6.D2-Emcys1 and one subcongenic line, D2.B6-Empsc1.1 from D2.B6-Empsc1 were developed to narrow down the critical region responsible for protoscolex development. From the results of infection experiments with E. multilocularis in these subcongenic mice, it is concluded that a gene responsible for protoscolex development is located between D1Mit290 (68.1 cM) and D1Mit511 (97.3 cM).
• An experimental study of menopause induced by bilateral ovariectomy and mechanistic effects of mesenchymal stromal cell therapy on the parotid gland of a rat model.

  Nesma Ibraheim El-Naseery, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon

  Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 220 9 - 20 0940-9602 2018/11 [Refereed][Not invited]
   

  The current study was conducted on a menopause rat model induced by ovariectomy to assess the histological and immunohistochemical alterations in the parotid glands and to verify the efficiency of human umbilical cord derived-mesenchymal stromal cell (hUCB-MSCs) in treating this condition. Eighteen adult female rats were equally divided into three groups: sham-operated (SHAM), ovariectomized (OVX) and OVX injected with hUCB-MSCs (OVX+hUCB-MSCs). At 3months post-ovariectomy, the salivary flow rate and size of the parotid glands were measured. The parotid glands were histologically investigated via H&E stained sections. Furthermore, immunohistochemical analysis for human CD105, human CD34, proliferating cell nuclear antigen (PCNA), single strand DNA (ssDNA), caspase 3, aquaporin (AQP)1, α-smooth muscle actin (α-SMA) and mouse CD34 were performed. The OVX group showed interstitial hemorrhage, dispersed acini and intracytoplasmic vacuoles in the acinar cells. Furthermore, immunohistochemical staining revealed a significant decrement in the number of ssDNA positive apoptotic cells, but a significant increment of PCNA positive proliferating cells, AQP1 positive blood capillaries, α-SMA positive myoepithelial cells and endogenous CD34 positive hematopoietic progenitor cells in the OVX+hUCB-MSCs group as compared with the OVX group. These findings suggest a potential regenerative therapy of MSCs to injured parotid gland structures. However, further investigations are required to illustrate the mechanism of hUCB-MSCs mediated parotid gland regeneration.
• Restricted localization of ultimobranchial body remnants and parafollicular cells in the one-humped camel (Camelus dromedarius).

  Teppei Nakamura, Yaser Hosny Ali Elewa, Osamu Ichii, Marina Hosotani, Wael A M Ghonimi, Osamu Tatsumi, Ken-Ichi Nagasaki, Yasuhiro Kon

  The Journal of veterinary medical science 80 (9) 1368 - 1372 0916-7250 2018/09/13 [Refereed][Not invited]
   

  Parafollicular cells (C-cells) exist within the thyroid glands and display different distributions within the glands among mammalian species. In the one-humped camel (Camelus dromedarius), localization of the C-cells remains under debate. We herein investigated appearance of C-cells and the remnants of the ultimobranchial body, origin of C-cells, in the thyroid glands of one-humped camels. Macroscopically, a white mass was present at one-third the length from the cranial end of the thyroid glands where the cranial thyroid artery entered. In addition, large fossae were frequently found adjacent to the white mass. Histologically, the mass was mainly composed of connective tissues, thyroid follicles, and two types of cell clusters: one was composed of cells with clear cytoplasm and the other was composed of non-keratinized epidermoid cells. The mass and the fossae contained p63-positive cells, indicating that they consisted of ultimobranchial body remnants. Calcitonin was expressed in cells with clear cytoplasm, which were localized just beneath the fossae and in the cell clusters of the white mass. C-cells also resided in both subfollicular and interfollicular spaces adjacent to the white mass, but gradually decreased toward the periphery. C-cells tended to display round shapes in the ultimobranchial body remnants and subfollicular spaces, and spindle shapes in interfollicular spaces. In conclusion, we demonstrated that the ultimobranchial body remnants were limited to the region around the entrance of cranial thyroid artery and vein, and C-cells were mainly concentrated within and around the ultimobranchial body remnants.
• Tissue-specific variation in 5'-terminal exons of mouse Anoctamin 1 transcript induces N-terminal variation of its protein via alternative translational start sites.

  Akihiro Kamikawa, Junpei Sakazaki, Osamu Ichii

  Biochemical and biophysical research communications 503 (3) 1710 - 1715 0006-291X 2018/09/10 [Refereed][Not invited]
   

  Anoctamin 1 (encoded by the Ano1 gene) is a Ca2+-activated Cl- channel critical to many physiological functions. It has been speculated that Ano1 expression is regulated in a tissue-dependent manner via alternative promoters. However, variation in the 5'-end sequence of mouse Ano1 (mAno1) and its tissue-dependent regulation are poorly understood. We identified a novel 5'-terminal exon (designated exon 1a) of mAno1 instead of the known 5'-terminal exon (exon 0) using 5'-rapid amplification of cDNA ends (RACE) analysis. Unexpectedly, the novel 5'-end variant mAno1Ex1a was abundantly expressed in many tissues including the salivary and mammary glands, rectum, lung, trachea and prostate. In contrast, the known variant mAno1Ex0 predominated only in male reproductive tissues such as the epididymis and testis. In a heterologous expression system, mAno1Ex0 encoded a longer protein than mAno1Ex1a, and this long isoform was abolished by a mutation in the exon 0 start codon. Moreover, the mAno1Ex0-specific N-terminal sequence was immunohistochemically detected in epididymis but not in salivary gland. Our data suggest that mAno1 expression is regulated via alternative promoters, and its transcriptional variation results in variation of the N-terminal sequence of the Ano1 protein due to the alternative translation initiation sites. These tissue-specific variations might contribute to the regulation of mAno1 expression and activity according to the physiological function of each tissue.
• Wall thickness control in biotubes prepared using type-C mold.

  Takeshi Terazawa, Takanori Nishimura, Tomohiro Mitani, Osamu Ichii, Teppei Ikeda, Keigo Kosenda, Eisuke Tatsumi, Yasuhide Nakayama

  Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs 21 (3) 387 - 391 1434-7229 2018/09 [Refereed][Not invited]
   

  A type-C mold based on in-body tissue architecture was previously developed for preparing small-diameter biotube vascular grafts with a 2-mm diameter and approximately 1-mm wall thickness. In this study, the type-C mold was modified for preparing large-diameter biotubes with controlled wall thicknesses. Four types of molds were assembled by inserting silicone center rods (outer diameters 11, 13, 15, 17 mm) into stainless steel cages (inner diameter 19 mm) and surgically embedded in the abdominal subcutaneous pouches of Holstein cows. After 8-12 weeks, connective tissues occupied the rod-cage gap in the molds to form biotubes. The wall thickness of the biotubes obtained after removing the molds was approximately 1-3 mm, which corresponded to approximately 80% of each gap distance. The breaking strength almost linearly increased with the wall thickness of the biotubes. The strength of the biotubes with wall thickness over 1.5 mm was higher than that of beagle blood vessels. The thickest biotubes were as strong as bovine pericardium and can be used as an alternative trachea graft because of their adequate lumen-holding force.
• Abnormal Morphology of Distal Tubular Epithelial Cells Is Regulated by Genetic Factors Derived from Mouse Chromosome 12.

  Osamu Ichii, Teppei Nakamura, Taro Horino, Akira Yabuki, Yaser H A Elewa, Yasuhiro Kon

  The American journal of pathology 188 (9) 2120 - 2138 0002-9440 2018/09 [Refereed][Not invited]
   

  The distal tubule (DT) helps regulate blood pressure and electrolytes. We describe a novel, autosomal recessive, morphofunctional DT abnormality in inbred mice evident as columnar alternations and age-related cystic changes. This abnormality developed in both sexes of DBA/2Cr. Similar phenotypes were observed in A/J, C3H/He, DBA/1J, and FVB/N strains, but not in AKR/N, BALB/c, or C57BL/6N strains. In DBA/2Cr, abnormal DT localized to straight and convoluted segments and showed IL-36α DT injury marker expression. However, DT epithelial proliferation, examined by bromodeoxyuridine incorporation, was not remarkably altered with the progression of abnormality. Abnormal DT epithelial cells in DBA/2Cr displayed elongated primary cilia, loose intercellular adhesions, and numerous vesicles with altered localization of CD9, Na+/K+ATPase, and E-cadherin, indicating altered cell function, adhesion, and polarity. DBA/2Cr-type D12Mit182-D12Mit83 was identified as a candidate locus designated DBA/2 renal cyst (drecy). Within drecy, the gene regulated by estrogen in breast cancer protein (Greb1) transcript variant 2 was significantly up-regulated in DBA/2Cr kidney versus C57BL/6N. Greb1 localized to DT cytoplasm in C57BL/6 and to cytoplasm and nucleus in DBA/2Cr. Greb1-overexpressing M-1 kidney cells showed an altered epithelial-mesenchyme phenotype. B6.D2-(D12Mit182-D12Mit83) congenic mice carrying drecy did not show DT abnormalities, whereas DBA/2Cr × B6.D2-(D12Mit182-D12Mit83) mice did. Identification of this novel DT abnormality regulated by a DBA/2Cr mouse chromosome 12-derived locus and additional genetic factors improve the understanding of DT pathogenesis.
• Modified scanning electron microscopy reveals pathological crosstalk between endothelial cells and podocytes in a murine model of membranoproliferative glomerulonephritis.

  Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yuki Otani, Marina Hosotani, Yasuhiro Kon

  Scientific reports 8 (1) 10276 - 10276 2018/07/06 [Refereed][Not invited]
   

  This study evaluated endothelial cells and podocytes, both being primary components of the glomerular filtration barrier, in the progression of membranoproliferative glomerulonephritis (MPGN) using modified scanning electron microscopy (mSEM) analysis. BXSB/MpJ-Yaa model mice exhibited autoimmune-mediated MPGN characterised by elevated serum autoantibody levels, albuminuria, renal dysfunctional parameters, and decreased glomerular endothelial fenestrations (EF) and podocyte foot process (PFP) effacement with immune cell infiltration. Similar to transmission electron microscopy, mSEM revealed a series of pathological changes in basement membrane and densities of EF and PFP in BXSB/MpJ-Yaa compared with control BXSB/MpJ at different stages. Further, immunopositive area of endothelial marker (CD34), podocyte functional molecules (Nephrin, Podocin, Synaptopodin, and Wilms' tumour 1 (WT1)), and vascular endothelial growth factor A (VEGF A) significantly decreased in the glomerulus of BXSB/MpJ-Yaa compared with BXSB at final stage. The indices of glomerular endothelial injuries (EF density and immunopositive area of CD34 and VEGF A) and podocyte injuries (PEP density and immunopositive area of podocyte functional molecules) were also significantly correlated with each other and with indices of autoimmune disease and renal dysfunction. Thus, our results elucidated the pathological crosstalk between endothelial cells and podocytes in MPGN progression and the usefulness of mSEM for glomerular pathological analysis.
• Pulmonary hypertension due to unclassified interstitial lung disease in a Pembroke Welsh corgi.

  Tomoya Morita, Kensuke Nakamura, Tatsuyuki Osuga, Atsushi Kobayashi, Osamu Ichii, Akira Yabuki, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 80 (6) 939 - 944 0916-7250 2018/06/29 [Refereed][Not invited]
   

  A 12 year-old intact male Pembroke Welsh corgi weighing 10.8 kg was presented for evaluation of a 3-month history of dyspnea, and a 1-week history of exercise intolerance and anorexia. Severe hypoxemia (PaO2 56 mmHg), diffuse lung alveolar infiltration, and severe pulmonary hypertension (PH) (tricuspid regurgitation pressure gradient was 81 mmHg) were identified. A tentative diagnosis of severe PH due to lung disease or pulmonary thromboembolism was made and treated intensively. After 5 days of hospitalization, the dog died despite oxygen supplementation and anticoagulant therapy. This dog was diagnosed as unclassified interstitial lung disease based on histopathological findings.
• Macrophage activation syndrome associated with systemic lupus erythematosus treated successfully with the combination of steroid pulse, immunoglobulin and tacrolimus.

  Natsuki Aoyama-Maeda, Taro Horino, Osamu Ichii, Yoshio Terada

  Romanian journal of internal medicine = Revue roumaine de medecine interne 56 (2) 117 - 121 1220-4749 2018/06/01 [Refereed][Not invited]
   

  Macrophage activation syndrome (MAS), a variant of secondary hemophagocyticlymphohistiocytosis, is a potentially life-threatening complication of inflammatory and autoimmune diseases. We present a case of MAS as a rare manifestation of systemic lupus erythematosus. Although initial treatment with corticosteroid, with or without cyclosporine A, is justified in patients with MAS, evidence regarding the effectiveness of this treatment protocol remains to be clarified. Our patient was successfully treated with a combination of intravenous immunoglobulin therapy and intravenous methyl predonisolone pulse therapy, which was followed by a course of oral prednisolone and oral tacrolimus. Based on our experience, we propose tacrolimus to provide a more useful adjuvant treatment to corticosteroid therapy than cyclosporine A.
• Cotton rats (Sigmodon hispidus) possess pharyngeal pouch remnants originating from different primordia.

  Teppei Nakamura, Osamu Ichii, Takao Irie, Tatsuya Mizoguchi, Akio Shinohara, Hirokazu Kouguchi, Yuji Sunden, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Chihiro Koshimoto, Ken-Ichi Nagasaki, Yasuhiro Kon

  Histology and histopathology 33 (6) 555 - 565 0213-3911 2018/06 [Refereed][Not invited]
   

  Pharyngeal pouches in mammals develop into specific derivatives. If the differentiation of the pharyngeal pouches is anomalous, their remnants can result in cysts, sinuses, and fistulae in the differentiated organs or around the neck. In the present study, we found several pharyngeal pouch remnants, such as cystic structures in thymus and parathyroid gland and fossulae extended from the piriform fossa, in the inbred cotton rats maintained at Hokkaido Institute of Public Health (HIS/Hiph) and University of Miyazaki (HIS/Mz). In HIS/Hiph, the fossulae extended from the apex of the piriform fossa into the thyroid glands and were lined with stratified squamous and cuboidal epithelium. Calcitonin-positive C-cells were present within their epithelium in HIS/Hiph. In contrast, the fossulae of HIS/Mz ran outside the thyroid glands toward the parathyroid glands; they were lined with columnar ciliated epithelium and a few goblet cells, but had no C-cells, which was consistent with the cystic structures in the thymus and the parathyroid gland. These results indicated that the fossulae were a remnant of the ultimobranchial body in HIS/Hiph and of the thymopharyngeal duct in HIS/Mz. Thus, the fossulae of the piriform fossa resembled the piriform sinus fistula in human. In conclusion, cotton rats frequently possessed pharyngeal pouch remnants, including the piriform sinus fistula, and therefore, might serve as a novel model to elucidate the mechanisms of pharyngeal pouch development.
• Intestinal Spirochetosis Caused by Brachyspira pilosicoli in a Systemic Lupus Erythematosus Patient.

  Eguchi T, Inoue K, Horino T, Matsumoto T, Kamioka S, Nishida Y, Morimoto M, Morimoto N, Ichii O, Terada Y

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 1076-1608 2018/06 [Refereed][Not invited]
  
• A case of acute kidney injury caused by granulomatous interstitial nephritis associated with sarcoidosis.

  Taro Horino, Tatsuki Matsumoto, Kosuke Inoue, Osamu Ichii, Yoshio Terada

  CEN case reports 7 (1) 34 - 38 2018/05 [Refereed][Not invited]
   

  Sarcoidosis affects multiple organs including lung, heart and kidney. Sarcoidosis causes hypercalcemia, hypergammaglobulinemia, and rarely, granulomatous interstitial nephritis, resulting in renal stromal damage. Granulomatous interstitial nephritis is characterized as interstitial nephritis with noncaseating epithelioid granulomas. Diagnosing granulomatous interstitial nephritis before patient's death is challenging; hence, only few cases proven by renal biopsy have been reported till date. We present a case of acute kidney injury caused by granulomatous interstitial nephritis as a renal manifestation of sarcoidosis proven by renal biopsy, which can be confirmed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Glucocorticoid therapy was helpful for improving and maintaining her renal function over a 6-year period.
• A glycomics approach to discover novel renal biomarkers in birds by administration of cisplatin and diclofenac to chickens.

  C Ishii, Y Ikenaka, O Ichii, S M M Nakayama, S-I Nishimura, T Ohashi, M Tanaka, H Mizukawa, M Ishizuka

  Poultry science 97 (5) 1722 - 1729 0032-5791 2018/05/01 [Refereed][Not invited]
   

  Avian species have a unique renal structure and abundant blood flow into the kidneys. Although many birds die due to nephrotoxicity caused by chemicals, there are no early biomarkers for renal lesions. Uric acid level in blood, which is generally used as a renal biomarker, is altered when the kidney function is damaged by over 70%. Therefore, early biomarkers for kidney injury in birds are needed. In humans, glycomics has been at the forefront of biological and medical sciences, and glycans are used as biomarkers of diseases, such as carcinoma. In this study, a glycomics approach was used to screen for renal biomarkers in chicken. First, a chicken model of kidney damage was generated by injection of diclofenac or cisplatin, which cause acute interstitial nephritis (AIN) and acute tubular necrosis (ATN), respectively. The nephrotoxicity levels were determined by a blood chemical test and histopathological analysis. The plasma N-glycans were then analyzed to discover renal biomarkers in birds. Levels of 14 glycans increased between pre- and post administration in kidney-damaged chickens in the diclofenac group, and some of these glycans had the same presumptive composition as those in human renal carcinoma patients. Glycan levels did not change remarkably in the cisplatin group. It is possible that there are changes in glycan expression due to AIN, but they do not reflect ATN. Although further research is needed in other species of birds, glycans are potentially useful biomarkers for AIN in avian species.
• Effects of topiroxostat in hyperuricemic patients with chronic kidney disease.

  Taro Horino, Yutaka Hatakeyama, Osamu Ichii, Tatsuki Matsumoto, Yoshiko Shimamura, Kosuke Inoue, Yoshio Terada, Yoshiyasu Okuhara

  Clinical and experimental nephrology 22 (2) 337 - 345 1342-1751 2018/04 [Refereed][Not invited]
   

  BACKGROUND: Hyperuricemia is associated with chronic kidney disease (CKD). Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has a strong effect against hyperuricemia, limited data are available on its renoprotective effect against CKD. METHODS: This study was conducted between October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered 40 mg/day of topiroxostat twice daily. All patients were followed for a year. To elucidate the effects of topiroxostat, we evaluated the clinically documented primary indication of progression, viz. laboratory evidence of kidney function decline (reference indicator), uric acid, and hypertension in different patient groups, separated according to their baseline uProt levels and baseline eGFR. RESULTS: Topiroxostat treatment resulted in significant reduction in SUA (-1.53 mg/dL), systolic blood pressure (-8.9 mmHg), diastolic blood pressure (-5.0 mmHg), and urinary protein excretion (-795.5 mg/gCr) compared with baseline values. However, serum creatinine and urinary NAG levels, and estimated glomerular filtration rate did not change significantly. CONCLUSIONS: Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect in hyperuricemic patients with CKD. Further studies are required to clarify whether topiroxostat prevents the progression of renal disease and improves the prognosis of CKD patients.
• The First Case of Lupus Nephritis Developing in a Patient With Mantle Cell Lymphoma.

  Taro Horino, Yuki Osakabe, Mio Matsuura, Osamu Ichii, Yoshio Terada

  Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 24 (3) 159 - 164 1076-1608 2018/04 [Refereed][Not invited]
  
• Renal thrombotic microangiopathy caused by bevacizumab.

  Taro Horino, Osamu Ichii, Yoshiko Shimamura, Yoshio Terada

  Nephrology (Carlton, Vic.) 23 (4) 378 - 379 1320-5358 2018/04 [Refereed][Not invited]
  
• Changes in Renal Peritubular Capillaries in Canine and Feline Chronic Kidney Disease.

  R Nakamura, A Yabuki, O Ichii, H Mizukawa, N Yokoyama, O Yamato

  Journal of comparative pathology 160 79 - 83 0021-9975 2018/04 [Refereed][Not invited]
   

  Renal capillary rarefaction is a crucial event that leads to tubulointerstitial damage during the progression of chronic kidney disease (CKD). In the present study, changes in CD34-positive renal capillaries were investigated in dogs and cats with CKD. A significant decrease in CD34-positive capillaries was observed in canine diseased kidneys, even at the early stage of disease. In cats, CD34-positive capillaries were well preserved in the diseased kidneys, with no link to the severity of CKD. Renal capillary rarefaction might be a trigger event that leads to the progression of CKD in dogs, rather than in cats.
• Bilateral striopallidodentate calcinosis associated with Sjögren's syndrome and IgDλ monoclonal gammopathy of undetermined significance.

  Taro Horino, Tatsuki Matsumoto, Kosuke Inoue, Osamu Ichii, Yoshio Terada

  Joint bone spine 85 (2) 243 - 245 1297-319X 2018/03 [Refereed][Not invited]
   

  We presented the first case of bilateral striopallidodentate calcinosis secondary to Sjögren's syndrome. Further consideration should be given to the association between Sjögren's syndrome and bilateral striopallidodentate calcinosis, because Sjögren's syndrome is latent, but more frequent than other autoimmune diseases.
• Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

  Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Kozue Sotozaki, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Experimental biology and medicine (Maywood, N.J.) 243 (5) 418 - 427 1535-3702 2018/03 [Refereed][Not invited]
   

  Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall population has led to a concomitant age-related increase in chronic kidney disease. Moreover, the global prevalence of patients with chronic kidney disease is gradually increasing, which poses a serious public health problem. The limited number of spontaneous chronic kidney disease animal models, which resemble chronic kidney disease pathogenesis in elderly individuals, is a major limitation in the development of experimental and curative medicines for chronic kidney disease. This pathological study clarified that sex-related factors, including hormones, and abnormalities of the female reproductive system, such as pyometra, are closely associated with chronic kidney disease development by using cotton rats ( Sigmodon hispidus). Further, ovariectomy inhibited the phenotypes of the female reproductive system, immunological abnormalities, and chronic kidney disease. Thus, this laboratory rodent serves as a novel and useful spontaneous chronic kidney disease model to elucidate the candidate disease factors and the pathogenesis of chronic kidney disease both in human and experimental medicine.
• A case of neuronal intranuclear inclusion disease associated with lupus nephritis-like nephropathy.

  Taro Horino, Tatsuki Matsumoto, Kosuke Inoue, Osamu Ichii, Yoshio Terada

  eNeurologicalSci 10 28 - 30 2018/03 [Refereed][Not invited]
   

  Neuronal intranuclear inclusion disease (NIID) is a relatively new entity identified as a progressive neurodegenerative disease characterised by eosinophilic hyaline intranuclear inclusions widely observed in neuronal and somatic cells. Renal biopsy from one of our patients with NIID showed lupus nephritis-like pathology. He was treated with steroids and angiotensin-converting enzyme inhibitors and his proteinuria improved. The present case highlights that immune-mediated glomerulonephritis can be a presenting feature of NIID, which can be controlled with proper treatment.
• Autoimmune abnormality affects ovulation and oocyte-pick-up in MRL/MpJ-Fas lpr/lpr mice.

  M Hosotani, O Ichii, T Nakamura, S O Kanazawa, Y Hosny Ali Elewa, Y Kon

  Lupus 27 (1) 82 - 94 0961-2033 2018/01 [Refereed][Not invited]
   

  Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas lpr/lpr mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of "oocyte cumulus complexes" found in the ampulla was macroscopically counted, and that of "ovulated oocytes" was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas lpr/lpr mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas lpr/lpr mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas lpr/lpr mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.
• MicroRNAs associated with the development of kidney diseases in humans and animals.

  Osamu Ichii, Taro Horino

  Journal of toxicologic pathology 31 (1) 23 - 34 0914-9198 2018/01 [Refereed][Not invited]
   

  Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18-25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing. Particularly, miR-21 seems to be strongly associated with renal pathogenesis both in the glomerulus and tubulointerstitium. Furthermore, abundant evidence has been gathered showing the involvement of miRNAs in renal fibrosis. Because of the complex morphofunctional organization of the mammalian kidneys, it is crucial both to determine the exact localization of the kidney cells that express the miRNAs, which has been addressed mainly using in situ hybridization methods, and to identify precisely which mRNAs are bound and degraded by these miRNAs, which has been studied mostly through in vitro analysis. To discover novel biomarker candidates, miRNA levels in urine supernatant, sediment, and exosomal fraction were comprehensively investigated in different types of kidney disease, including drug-induced AKI, ischemia-induced AKI, diabetic nephropathy, lupus nephritis, and IgA nephropathy. Recent studies also demonstrated the therapeutic effect of miRNA and/or anti-miRNA administrations. The intent of this review is to illustrate the state-of-the-art research in the field of miRNAs associated with renal pathogenesis, especially focusing on AKI and CKD in humans and animal models.
• Histopathological Correlations between Mediastinal Fat-Associated Lymphoid Clusters and the Development of Lung Inflammation and Fibrosis following Bleomycin Administration in Mice.

  Yaser Hosny Ali Elewa, Osamu Ichii, Kensuke Takada, Teppei Nakamura, Md Abdul Masum, Yasuhiro Kon

  Frontiers in immunology 9 271 - 271 2018 [Refereed][Not invited]
   

  Bleomycin (BLM) has been reported to induce lung inflammation and fibrosis in human and mice and showed genetic susceptibility. Interestingly, the C57BL/6 (B6) mice had prominent mediastinal fat-associated lymphoid cluster (MFALCs) under healthy condition, and showed susceptibility to development of lung fibrosis following BLM administration. However, the pathogenesis of lung lesion progression, and their correlation with MFALC morphologies, remain to be clarified. To investigate the correlations between MFALC structures and lung injuries in B6 mice, histopathological examination of mediastinal fat tissues and lungs was examined at 7 and 21 days (d) following a single 50 μL intranasal (i.n.) instillation of either BLM sulfate (5 mg/kg) (BLM group) or phosphate-buffered saline (control group). The lung fibrosis was examined by Masson's trichrome (MT) stain of paraffin sections and mRNA expression levels of Col1a1, Col3a1, and Acta2 in different frozen lung samples. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1, BrdU, LYVE-1, and peripheral node addressin (PNAd) was performed to detect T- and B-cells, macrophages, granulocytes, proliferating cells, lymph vessels (LVs), and high endothelial venules (HEVs). We found that MFALCs were more abundant in the BLM group as compared to the control group. The lung of BLM group developed pneumonitis with severe cellular infiltrations at 7 days and significant collagen deposition (MT) and higher expression of Col1a1, and Col3a1 at 21 days post-administration. Numerous immune cells, proliferating cells, HEVs, and LVs were observed in both MFALCs and lungs of the BLM group. Interestingly, PNAd + HEVs were observed in the lungs of the BLM group, but not the control group. Moreover, numerous Gr1 + polymorphonuclear and mononuclear-like ring cells were found in the MFALCs and lungs of the BLM group. Interestingly, flow cytometric analysis revealed a significant increase of B-cell populations within the MFALCs of BLM group suggesting a potential proliferative induction of B-cells following inflammation. Furthermore, significant positive correlations were observed between quantitative parameters of these immune cells in both the lungs and MFALCs. Thus, we suggest a potentially important role for MFALCs and HEVs in the progression of lung disease, especially in inflammatory lung disease.
• Ovarian mast cells migrate toward ovary-fimbria connection in neonatal MRL/MpJ mice.

  Teppei Nakamura, Masataka Chihara, Osamu Ichii, Saori Otsuka-Kanazawa, Ken-Ichi Nagasaki, Yaser Hosny Ali Elewa, Osamu Tatsumi, Yasuhiro Kon

  PloS one 13 (4) e0196364  2018 [Refereed][Not invited]
   

  MRL/MpJ mice have abundant ovarian mast cells (MCs) as compared with other strains at postnatal day 0 (P0); however, they sharply decrease after birth. These ovarian MCs, particularly beneath the ovarian surface epithelium (SE), which express mucosal MC (MMC) marker, might participate in early follicular development. This study investigated the changes in spatiotemporal distribution of MCs in the perinatal MRL/MpJ mouse ovaries. At P0 to P7, the MCs were densely localized to the ovary, especially their caudomedial region around the ovary-fimbria connection. The neonatal ovarian MCs showed intermediate characteristics of MMC and connective tissue MC (CTMC), and the latter phenotype became evident with aging. However, the expression ratio of the MMC to CTMC marker increased from P0 to P4 in the MRL/MpJ mouse ovary. Similarly, the ratio of MCs facing SE to total MC number increased with aging, although the number of ovarian MCs decreased, indicating the relative increase in MMC phenotypes in the early neonatal ovary. Neither proliferating nor apoptotic MCs were found in the MRL/MpJ mouse ovaries. The parenchymal cells surrounding MCs at ovary-fimbria connection showed similar molecular expression patterns (E-cadherin+/Foxl2-/Gata4+) as that of the ovarian surface epithelial cells. At P2, around the ovary-fimbria connection, c-kit- immature oocytes formed clusters called nests, and some MCs localized adjacent to c-kit- oocytes within the nests. These results indicated that in postnatal MRL/MpJ mice, ovarian MCs changed their distribution by migrating toward the parenchymal cells composing ovary-fimbria connection, which possessed similar characteristics to the ovarian surface epithelium. Thus, we elucidated the spatiotemporal alterations of the ovarian MCs in MRL/MpJ mice, and suggested their importance during the early follicular development by migrating toward the ovary-fimbria connection. MRL/MpJ mice would be useful to elucidate the relationship between neonatal immunity and reproductive systems.
• Morphofunctional analysis of antigen uptake mechanisms following sublingual immunotherapy with beads in mice.

  Yaser Hosny Ali Elewa, Tatsuya Mizoguchi, Osamu Ichii, Teppei Nakamura, Yasuhiro Kon

  PloS one 13 (12) e0201330  1932-6203 2018 [Refereed][Not invited]
   

  BACKGROUND: Recently, sublingual immunotherapy (SLIT) has been used as a safe and efficient method for the treatment of and immunization against asthma and various allergies. However, the routes of antigen/allergen (particulate antigen) uptake through the mucosa of the oral cavity remain incompletely understood, as do the roles of sex and age in the process. For this purpose, to elucidate the mechanism and efficacy of SLIT among different sexes and ages, microbeads were dripped into the sublingual region to mimic particulate antigen uptake by the sublingual mucosa. METHODS: Twenty microliters of either phosphate buffered saline (PBS) or fluorescently labelled microbeads (latex and silica beads) were placed under the tongue of both male and female C57BL/6 mice at young (3 months) and old (6 months) ages. The lower jaw was examined 30 min after administration, and beads were detected with a fluorescence stereomicroscope. Morphological observations of the mucosa of the fluorescent areas were made with a scanning electron microscope (SEM) and an all-in-one light fluorescence microscope (LM). Fluorescence intensity was compared between both sexes and ages. RESULTS: Stereomicroscopic observation revealed fluorescent illuminations in three compartments of the sublingual mucosa: the sublingual caruncles (SC), the oral rostral mucosa (OR) and the buccal mucosa (BM). Interestingly, the fluorescence intensity tended to be higher among females than among males in the SC region in particular. However, there were no significant age-related differences. SEM and LM revealed beads in the lumina of both mandibular ducts and sublingual ducts (Sd). Additionally, the apical cytoplasm of some Sd cells contained silica beads. However, there was no specification in the OR mucosa or BM. CONCLUSIONS: This study reveals the major role Sd plays in local immunity via the antigen uptake mechanisms. Furthermore, our data suggest that the efficacy of SLIT in humans could be affected by sex.
• Urinary Exosome-Derived microRNAs Reflecting the Changes in Renal Function in Cats.

  Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Frontiers in veterinary science 5 289 - 289 2018 [Refereed][Not invited]
   

  Increased incidence of kidney disease (KD) is a common concern in human and companion animals. Cats, in particular, are highly susceptible to KD. Novel KD biomarkers would help to address these problems. Therefore, we are focusing on microRNA, a highly conserved nucleic acid, as a KD biomarker for various animals. We previously reported that altered levels of urinary exosome (UExo)-derived microRNAs indicate renal pathologies in dogs. This study comprehensively examined UExo-derived microRNAs, which reflected the KD status in cats. The examined cats were divided into two groups: normal renal function (NR) and KD. Based on our previous data in dogs and cats, as well as the present data on UExo-derived microRNAs in cats by next-generation sequencing, let-7b, let-7f, miR-10a, miR-10b, miR-21a, miR-22, miR-26a, miR-27b, miR-146a, miR-181a, miR-191, and miR-486a were identified as biomarker candidates. In summary, the levels of UExo-derived let-7b, miR-22, and miR-26a significantly decreased in cats with KD from the early stages of the disease. UExo-derived miRNA levels normalized to urinary creatinine or total RNA of miR-21a was significantly higher in the KD group. Importantly, the ratio of UExo-derived miR-21a to let-7b showed a significant and strongest correlation with serum creatinine (ρ = 0.751), blood urea nitrogen (ρ = 0.754), and urinary creatinine (ρ = -0.421) among all examined indices. Further, the ratio of miR-181a to let-7b or miR-10b significantly correlated with the progression of renal dysfunction in the KD group. Thus, we identified that UExo-derived microRNAs in cats, and their raw and normalized levels could indicate altered renal function.
• First molecular detection of Sarcocystis ovalis in the intestinal mucosa of a Japanese jungle crow (Corvus macrorhynchos) in Hokkaido, Japan.

  Takao Irie, Tetsuya Ikeda, Teppei Nakamura, Osamu Ichii, Noriko Yamada, Takuya Ito, Akiko Yamazaki, Shinji Takai, Kinpei Yagi

  Veterinary parasitology, regional studies and reports 10 54 - 57 2017/12 [Refereed][Not invited]
   

  Although cysts of Sarcocystis spp. have been detected in domestic and wild animals throughout Japan, their natural definitive hosts have not been fully elucidated. Additionally, in Hokkaido, several Sarcocystis spp. are highly prevalent among wild sika deer (Cervus nippon yesoensis), one of which is S. ovalis. The life cycle of S. ovalis is maintained in corvid birds. To identify the definitive host for S. ovalis in Hokkaido, we investigated its prevalence among corvid birds (Corvus macrorhynchos and C. corone). A total of 42 crow carcasses were collected during August 2015-July 2016 in southern Hokkaido. Examination for coccidian sporocysts in rectal feces and intestinal mucosa, detection of Sarcocystis DNA (18S rRNA gene) from intestinal mucosa samples, and histological observation of intestinal tissue were conducted. No Sarcocystis sporocysts were detected in fecal and mucosal samples by flotation. DNA from intestinal mucosa was positive in one crow (C. macrorhynchos). Phylogenetic analysis demonstrated the isolate clustered with S. ovalis and was closely related to isolates obtained from sika deer in Hokkaido. Histologically, S. ovalis gamogenesis (gamonts or gametes) and oocyst production were observed in the villi of the crow positive for S. ovalis DNA. However, the crow was negative for other coccidian parasites, such as Eimeria, by fecal examination. Our results suggested that crows harbor S. ovalis in the intestine and may serve as a definitive host of S. ovalis in Hokkaido. To our knowledge, this is the first report on a natural definitive host for Sarcocystis spp. prevalent among sika deer in Japan.
• PMab-52: Specific and Sensitive Monoclonal Antibody Against Cat Podoplanin for Immunohistochemistry.

  Shinji Yamada, Shunsuke Itai, Takuro Nakamura, Miyuki Yanaka, Noriko Saidoh, Yao-Wen Chang, Saori Handa, Hiroyuki Harada, Yumiko Kagawa, Osamu Ichii, Satoru Konnai, Mika K Kaneko, Yukinari Kato

  Monoclonal antibodies in immunodiagnosis and immunotherapy 36 (5) 224 - 230 2017/10 [Refereed][Not invited]
   

  Podoplanin (PDPN) is expressed in several normal tissues, such as lymphatic endothelial cells, podocytes of renal glomerulus, and type I alveolar cells of lung. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet. Although monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, rabbit PDPN, dog PDPN, and bovine PDPN have been established, anticat PDPN (cPDPN) mAbs have not been developed. In this study, we immunized mice with Chinese hamster ovary (CHO)-K1 cell lines expressing cPDPN, and developed anti-cPDPN mAbs. One of the clones, PMab-52 (IgM, kappa), detected cPDPN specifically in flow cytometry and Western blot analysis. PMab-52 is also useful for detecting feline squamous cell carcinoma cells in immunohistochemical analysis. PMab-52 is expected to be useful for investigating the function of cPDPN in feline carcinomas.
• Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

  Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yasuhiro Kon

  BMC nephrology 18 (1) 280 - 280 1471-2369 2017/09/04 [Refereed][Not invited]
   

  BACKGROUND: The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. METHODS: Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). RESULTS: Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34+ glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34+ tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34+ glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. CONCLUSIONS: From the analysis of mouse models, we identified inverse pathological correlations between the number of local capillaries in GLs and TILs and the severity of kidney diseases.
• Macromolecular creatine kinase type 1 in immune-mediated necrotizing myopathy.

  T Horino, O Ichii, K Ode-Hamada, Y Terada

  QJM : monthly journal of the Association of Physicians 110 (9) 593 - 594 1460-2725 2017/09/01 [Refereed][Not invited]
  
• Sex-related differences in autoimmune-induced lung lesions in MRL/MpJ-faslpr mice are mediated by the development of mediastinal fat-associated lymphoid clusters.

  Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon

  Autoimmunity 50 (5) 306 - 316 0891-6934 2017/08 [Refereed][Not invited]
   

  MRL/MpJ-Faslpr (lpr) mice are a model for autoimmune diseases such as systemic lupus erythematosus (SLE). These diseases mainly affect women, with a 10:1 female-to-male ratio, and cause pleuropulmonary lesions. We previously revealed a correlation between mediastinal fat-associated lymphoid cluster (MFALC) development and cellular infiltration in the lungs of lpr male mice; however, we did not report on MFALCs in females. The purpose of this investigation was to reveal sex-related differences in MFALCs in lpr mice. We compared the morphological features of MFALCs and lung mononuclear cell aggregates (LMCAs) in 5-month-old male and female lpr mice. The females showed significantly elevated anti-dsDNA autoantibody titers and larger MFALCs, with a higher ratio of lymphatic vessel (LV) and high endothelial venule (HEV) areas to MFALC area, and greater numbers of T- and B-cells, macrophages, and proliferating and dendritic cells in MFALCs and LMCAs than males. Our data indicated that MFALCs were more developed and lung lesions were more severe in female than in male lpr mice, thereby suggesting a potential role for LVs and HEVs in the establishment of MFALCs and lung lesions. Further investigation in female lpr mice will be needed for treatment of human respiratory diseases and autoimmune disorders.
• Effects of a mixture of medetomidine, midazolam and butorphanol on anesthesia and blood biochemistry and the antagonizing action of atipamezole in hamsters.

  Teppei Nakamura, Naoya Karakida, Ai Dantsuka, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon, Ken-Ichi Nagasaki, Hideki Hattori, Tomoji Yoshiyasu

  The Journal of veterinary medical science 79 (7) 1230 - 1235 0916-7250 2017/07/19 [Refereed][Not invited]
   

  Syrian golden hamsters (Mesocricetus auratus) are useful laboratory rodents for studying human infectious diseases, metabolic diseases and cancer. In other rodents, such as mice and rats, a mixture of medetomidine, midazolam and butorphanol functions as a useful anesthetic, although it alters some blood biochemical parameters. In this study, we examined the effects of this mixture on anesthesia and blood biochemical parameters, and the action of atipamezole, a medetomidine antagonist, in hamsters. Intramuscular injection of a mixture of medetomidine, midazolam and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, had a short induction time (within 5 min) and produced an anesthetic duration of approximately 100 min in hamsters. We also demonstrated that 0.15 mg/kg of atipamezole, corresponding to the same dose as medetomidine, made hamsters recover quickly from anesthesia. The anesthetic agent markedly altered metabolic parameters, such as plasma glucose and insulin; however, 0.15 mg/kg of atipamezole returned these levels to normal range within approximately 10 min after the injection. The anesthetic also slightly altered mineral levels, such as plasma inorganic phosphorus, calcium and sodium; the latter two were also improved by atipamezole. Our results indicated that the mixture of medetomidine, midazolam, and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, functioned as an effective anesthetic, and atipamezole was useful for antagonizing both anesthesia and biochemical alteration in hamsters.
• Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts.

  Tohru Yamamori, Tomoya Sasagawa, Osamu Ichii, Mie Hiyoshi, Tomoki Bo, Hironobu Yasui, Yasuhiro Kon, Osamu Inanami

  Journal of radiation research 58 (3) 292 - 301 0449-3060 2017/05/01 [Refereed][Not invited]
   

  Mitochondria strongly contribute to the maintenance of cellular integrity through various mechanisms, including oxidative adenosine triphosphate production and calcium homeostasis regulation. Therefore, proper regulation of the abundance, distribution and activity of mitochondria is crucial for the maintenance of cellular homeostasis. Previous studies have shown that ionizing radiation (IR) alters mitochondrial functions, suggesting that mitochondria are likely to be an important target of IR. Though IR reportedly influences cellular mitochondrial abundance, the mechanism remains largely unknown. In this study, we examined how IR influences mitochondrial abundance in mouse fibroblasts. When mouse NIH/3T3 cells were exposed to X-rays, a time-dependent increase was observed in mitochondrial DNA (mtDNA) and mitochondrial mass, indicating radiation-induced upregulation of mitochondrial abundance. Meanwhile, not only did we not observe a significant change in autophagic activity after irradiation, but in addition, IR hardly influenced the expression of two mitochondrial proteins, cytochrome c oxidase subunit IV and cytochrome c, or the mRNA expression of Polg, a component of DNA polymerase γ. We also observed that the expression of transcription factors involved in mitochondrial biogenesis was only marginally affected by IR. These data imply that radiation-induced upregulation of mitochondrial abundance is an event independent of macroautophagy and mitochondrial biogenesis. Furthermore, we found evidence that IR induced long-term cell cycle arrest and cellular senescence, indicating that these events are involved in regulating mitochondrial abundance. Considering the growing significance of mitochondria in cellular radioresponses, we believe the present study provides novel insights into understanding the effects of IR on mitochondria.
• Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.

  Shinji Yamada, Mika K Kaneko, Takuro Nakamura, Osamu Ichii, Satoru Konnai, Yukinari Kato

  Monoclonal antibodies in immunodiagnosis and immunotherapy 36 (2) 77 - 79 2017/04 [Refereed][Not invited]
   

  Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG2a, which was derived from rat PMab-1 mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.
• Hydronephrosis with ureteritis developed in C57BL/6N mice carrying the congenic region derived from MRL/MpJ-type chromosome 11.

  Osamu Ichii, Masataka Chihara, Shin-Hyo Lee, Teppei Nakamura, Saori Otsuka-Kanazawa, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Autoimmunity 50 (2) 114 - 124 0891-6934 2017/03 [Refereed][Not invited]
   

  Inbred MRL/MpJ mice show several unique phenotypes in tissue regeneration processes and the urogenital and immune systems. Clarifying the genetic and molecular bases of these phenotypes requires the analysis of their genetic susceptibility locus. Herein, hydronephrosis development was incidentally observed in MRL/MpJ-derived chromosome 11 (D11Mit21-212)-carrying C57BL/6N-based congenic mice, which developed bilateral or unilateral hydronephrosis in both males and females with 23.5% and 12.5% prevalence, respectively. Histopathologically, papillary malformations of the transitional epithelium in the pelvic-ureteric junction seemed to constrict the ureter luminal entrance. Characteristically, eosinophilic crystals were observed in the lumen of diseased ureters. These ureters were surrounded by infiltrating cells mainly composed of numerous CD3+ T-cells and B220+ B-cells. Furthermore, several Iba-1+ macrophages, Gr-1+ granulocytes, mast cells and chitinase 3-like 3/Ym1 (an important inflammatory lectin)-positive cells were detected. Eosinophils also accumulated to these lesions in diseased ureters. Some B6.MRL-(D11Mit21-D11Mit212) mice had duplicated ureters. We determined >100 single nucleotide variants between C57BL/6N- and MRL/MpJ-type chromosome 11 congenic regions, which were associated with nonsynonymous substitution, frameshift or stopgain of coding proteins. In conclusion, B6.MRL-(D11Mit21-D11Mit212) mice spontaneously developed hydronephrosis due to obstructive uropathy with inflammation. Thus, this mouse line would be useful for molecular pathological analysis of obstructive uropathy in experimental medicine.
• Localization of Toll-like Receptor (TLR) 2 and TLR4 mRNA in the Colorectal Mucosa of Miniature Dachshunds with Inflammatory Colorectal Polyps

  N. Yokoyama, H. Ohta, J. Yamazaki, Y. Kagawa, O. Ichii, N. Khoirun, T. Morita, T. Osuga, S. Y. Lim, N. Sasaki, K. Morishita, K. Nakamura, M. Takiguchi

  JOURNAL OF COMPARATIVE PATHOLOGY 156 (2-3) 183 - 190 0021-9975 2017/02 [Refereed][Not invited]
   

  Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay. Samples of inflamed colorectal mucosa (n = 5) and non-inflamed mucosa (n = 5) from miniature dachshunds (MDs) with ICRPs and colonic mucosa from healthy beagles (n = 5) were examined. TLR2 and TLR4 hybridization signals were localized to the colorectal epithelium, inflammatory cells and fibroblasts in the inflamed colorectal mucosa of affected dogs. The signals were significantly greater in inflamed colorectal epithelium compared with non-inflamed epithelium of MDs with ICRPs and healthy beagles (P <0.05). These results suggest that increased expression of TLR2 and TLR4 mRNA in the inflamed colorectal mucosa results from not only inflammatory cell infiltration, but also the upregulation of TLR2 and TLR4 mRNA in the colonic epithelium. (C) 2016 Elsevier Ltd. All rights reserved.
• Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs.

  Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Yuki Hoshino, Satoshi Takagi, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yasuhiro Kon

  Scientific reports 7 40340 - 40340 2045-2322 2017/01/11 [Refereed][Not invited]
   

  MicroRNAs act as post-transcriptional regulators, and urinary exosome (UExo)-derived microRNAs may be used as biomarkers. Herein, we screened for UExo-derived microRNAs reflecting kidney disease (KD) status in dogs. Examined dogs were divided into healthy kidney control (HC) and KD groups according to renal dysfunction. We confirmed the appearance of UExo having irregular globe-shapes in a dog by immunoblot detection of the exosome markers, TSG101 and CD9. Based on our previous data using KD model mice and the data obtained herein by next generation sequencing of UExo-derived microRNAs in dogs, miR-26a, miR-146a, miR-486, miR-21a, and miR-10a/b were selected as candidate microRNAs. In particular, UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, and miR-26a levels negatively correlated with deteriorated renal function compared to the other miRNAs. UExo-derived miR-21a levels corrected or not to that of internal control microRNAs in UExo, miR-26a and miR-191, significantly increased with renal dysfunction. In kidney tissues, the decrease of miR-26a and miR-10a/b in the glomerulus and miR-10b in the tubulointerstitium negatively correlated with deteriorated renal function and histopathology. Increased miR-21a in the tubulointerstitium rather than in the glomerulus correlated with deteriorated renal histopathology. In conclusion, microRNAs reflecting the changes in renal function and histopathology in dogs were identified in this study.
• IL-36α Regulates Tubulointerstitial Inflammation in the Mouse Kidney.

  Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Frontiers in immunology 8 1346 - 1346 1664-3224 2017 [Refereed][Not invited]
   

  IL-36α, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36α was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36α in kidney injury. IL-36α mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36α localized to dilated DTs. IL-36α expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36α+ DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36α receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36α stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36α-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36α-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36α overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36α may be a novel kidney injury marker useful for evaluating DT damages.
• Lipoma arborescens in a patient with pseudogout on hemodialysis.

  T Horino, T Matsumoto, Y Terada, O Ichii

  QJM : monthly journal of the Association of Physicians 109 (12) 827 - 828 1460-2725 2016/12 [Refereed][Not invited]
  
• Low expression of cyclooxygenase-2 in chronic kidney disease in young dogs.

  Akira Yabuki, Akiko Miyazaki, Osamu Ichii, Moeko Kohyama, Mariko Sawa, Osamu Yamato

  Research in veterinary science 109 71 - 73 0034-5288 2016/12 [Refereed][Not invited]
   

  Chronic kidney disease (CKD) often results in end-stage renal failure in young dogs; however, the pathogenesis of this disease is not established. This study investigated renal expression of cyclooxygenase (COX)-1 and COX-2 proteins in three dogs with chronic kidney disease by immunohistochemistry. Histopathology showed asynchronous differentiation of renal tissues, including immature glomeruli. COX-1 signals were not detected in diseased or normal kidneys. COX-2 signals were low or undetectable in diseased kidneys, while normal kidneys showed clear positive signals in the macula densa (MD). Quantitative scores of COX-2 in diseased kidneys were significantly lower than those in normal kidneys. These findings demonstrate low renal COX-2 expression in CKD in young dogs, but whether this is correlated with disease pathogenesis remains unclear.
• Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: A case report.

  Taro Horino, Osamu Ichii, Kazu Hamada-Ode, Tatsuki Matsumoto, Yoshiko Shimamura, Kosuke Inoue, Yoshio Terada

  Molecular and clinical oncology 5 (6) 693 - 696 2049-9450 2016/12 [Refereed][Not invited]
   

  Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is a rare neoplasm characterized by morphological analogy to papillary thyroid carcinoma and abnormal expression of thyroid transcription factor-1 (TTF-1). We herein report a rare case of TL-LGNPPA with a review of its clinical, morphological and immunohistochemical characteristics. The patient was a 25-year-old Japanese woman complaining of a 2-year history of fever of unknown origin. There were no remarkable physical findings and the laboratory tests, including C-reactive protein levels, were normal. Laryngoscopy, magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography identified a pedunculated mass at the roof of the nasopharynx. Histologically, the tumour exhibited papillary growth of cuboidal or columnar epithelium. Tubular architecture and a spindle cell component were also observed focally. Some tumour cells exhibited intranuclear cytoplasmic inclusions. Immunohistochemically, the neoplastic cells were positive for TTF-1, cytokeratin 7 and vimentin, but were negative for thyroglobulin. The Ki-67 labelling index (MIB-1 index) reached 5% in the most concentrated spot. The patient had neither local recurrence nor distant metastasis 3 years after removal of the tumour. In conclusion, TL-LGNPPA should be included it in the differential diagnosis of fever of unknown origin.
• Ca2+-activated Cl- channel currents in mammary secretory cells from lactating mouse.

  Akihiro Kamikawa, Osamu Ichii, Junpei Sakazaki, Toru Ishikawa

  American journal of physiology. Cell physiology 311 (5) C808-C819 - C819 0363-6143 2016/11/01 [Refereed][Not invited]
   

  The Cl- secretion via Ca2+-activated Cl- channel (CaCC) is critical for fluid secretion in exocrine glands like the salivary gland. Also in the mammary gland, it has been hypothesized that CaCC plays an important role in the secretion of Cl- and aqueous phase of milk. However, there has been no evidence for the functional expression of CaCC in native mammary secretory (MS) cells of lactating animals. We therefore assessed membrane current in MS cells that were freshly isolated from lactating mice using whole cell patch-clamp techniques. In MS cells, we detected CaCC current that exhibited the following characteristics: 1) Ca2+-dependent activation at the concentrations of submicromolar range; 2) voltage-dependent activation; 3) slow kinetics for activation and deactivation; 4) outward rectification of the steady-state current; 5) anion permeability in the sequence of I- > NO3- > Br- > Cl- > glutamate; 6) inhibition by Cl- channel blockers (niflumic acid, DIDS, and CaCCinh-A01). These characteristics of native CaCC current were similar to reported characteristics of heterologously expressed TMEM16A. RT-PCR analyses showed the expression of multiple CaCC channels including TMEM16A, Best1, and Best3 in the mammary glands of lactating mice. Immunohistochemical staining revealed the localization of TMEM16A protein at the apical membrane of the MS cells. Collectively, our data strongly suggest that MS cells functionally express CaCC, which is at least partly constituted by TMEM16A. The CaCC such as TMEM16A at the apical membrane of the MS cells may influence the quantity and/or quality of milk.
• Does the routine handling affect the phenotype of disease model mice?

  Maiko Ono, Hayato Sasaki, Kenichi Nagasaki, Daisuke Torigoe, Osamu Ichii, Nobuya Sasaki, Takashi Agui

  The Japanese journal of veterinary research 64 (4) 265 - 271 0047-1917 2016/11 [Refereed][Not invited]
   

  The three different mouse handling methods, picking up by tails, tunnels, and open hands were performed using the ICGN glomerulonephritis mouse and the severity of symptoms was evaluated. The handling groups exhibited a tendency of more severe symptoms than the non-handling control group. Female mice handled by their tails showed significantly more severe symptoms than the control group. In addition, we subjected the normal laboratory mice, C57BL/6 and BALB/c mice to tail and tunnel handling to assess the stress conditions. The plasma corticosterone level in the tail-handled mice was higher than that in control mice. These results indicate that handling causes stress and may affect the phenotype of disease model mice.
• Usefulness of an anesthetic mixture of medetomidine, midazolam, and butorphanol in cotton rats (Sigmodn hispidus).

  Teppei Nakamura, Osamu Ichii, Takao Irie, Marina Hosotani, Ai Dantsuka, Saori Nakamura, Shinobu Sato, Kozue Sotozaki, Hirokazu Kouguchi, Tomoji Yoshiyasu, Ken-Ichi Nagasaki, Yasuhiro Kon

  The Japanese journal of veterinary research 64 (4) 273 - 276 0047-1917 2016/11 [Refereed][Not invited]
   

  Tne cotton rat (Sigmodon hispidus) is a laboratory rodent used for studying human infectious diseases. However, a lack of suitable anesthetic agents inconveniences the use of cotton rats in surgical manipulation. This study demonstrated that subcutaneous injection of the mixture of medetomidine, midazolam, and butorphanol (0.15, 2.0, and 2.5 mg/kg, respectively), which is a suitable anesthetic agents for mice and rats, produced an anesthetic duration of more than 50 min in cotton rats. We also demonstrated that 0.15 mg/kg of atipamezole, an antagonist of medetomidine, produced a quick recovery from anesthesia in cotton rats. This indicated that the anesthetic mixture of medetomidine, midazolam, and butorphanol, functioned as a useful and effective anesthetic for short-term surgery in cotton rats.
• Degenerative and regenerative features of myofibers differ among skeletal muscles in a murine model of muscular dystrophy.

  Teppei Ikeda, Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Journal of muscle research and cell motility 37 (4-5) 153 - 164 0142-4319 2016/10 [Refereed][Not invited]
   

  Skeletal muscle myofibers constantly undergo degeneration and regeneration. Histopathological features of 6 skeletal muscles (cranial tibial [CT], gastrocnemius, quadriceps femoris, triceps brachii [TB], lumbar longissimus muscles, and costal part of the diaphragm [CPD]) were compared using C57BL/10ScSn-Dmd mdx (mdx) mice, a model for muscular dystrophy versus control, C57BL/10 mice. Body weight and skeletal muscle mass were lower in mdx mice than the control at 4 weeks of age; these results were similar at 6-30 weeks. Additionally, muscular lesions were observed in all examined skeletal muscles in mdx mice after 4 weeks, but none were noted in the controls. Immunohistochemical staining revealed numerous paired box 7-positive satellite cells surrounding the embryonic myosin heavy chain-positive regenerating myofibers, while the number of the former and staining intensity of the latter decreased as myofiber regeneration progressed. Persistent muscular lesions were observed in skeletal muscles of mdx mice between 4 and 14 weeks of age, and normal myofibers decreased with age. Number of muscular lesions was lowest in CPD at all ages examined, while the ratio of normal myofibers was lowest in TB at 6 weeks. In CT, TB, and CPD, Iba1-positive macrophages, the main inflammatory cells in skeletal muscle lesions, showed a significant positive correlation with the appearance of regenerating myofibers. Additionally, B220-positive B-cells showed positive and negative correlation with regenerating and regenerated myofibers, respectively. Our data suggest that degenerative and regenerative features of myofibers differ among skeletal muscles and that inflammatory cells are strongly associated with regenerative features of myofibers in mdx mice.
• Rapid specimen preparation to improve the throughput of electron microscopic volume imaging for three-dimensional analyses of subcellular ultrastructures with serial block-face scanning electron microscopy.

  Truc Quynh Thai, Huy Bang Nguyen, Sei Saitoh, Bao Wu, Yurika Saitoh, Satoshi Shimo, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon, Takashi Takaki, Kensuke Joh, Nobuhiko Ohno

  Medical molecular morphology 49 (3) 154 - 62 1860-1480 2016/09 [Refereed][Not invited]
   

  Serial block-face imaging using scanning electron microscopy enables rapid observations of three-dimensional ultrastructures in a large volume of biological specimens. However, such imaging usually requires days for sample preparation to reduce charging and increase image contrast. In this study, we report a rapid procedure to acquire serial electron microscopic images within 1 day for three-dimensional analyses of subcellular ultrastructures. This procedure is based on serial block-face with two major modifications, including a new sample treatment device and direct polymerization on the rivets, to reduce the time and workload needed. The modified procedure without uranyl acetate can produce tens of embedded samples observable under serial block-face scanning electron microscopy within 1 day. The serial images obtained are similar to the block-face images acquired by common procedures, and are applicable to three-dimensional reconstructions at a subcellular resolution. Using this approach, regional immune deposits and the double contour or heterogeneous thinning of basement membranes were observed in the glomerular capillary loops of an autoimmune nephropathy model. These modifications provide options to improve the throughput of three-dimensional electron microscopic examinations, and will ultimately be beneficial for the wider application of volume imaging in life science and clinical medicine.
• Female cotton rats (Sigmodon hispidus) develop chronic anemia with renal inflammation and cystic changes.

  Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Daisuke Nakamura, Saori Nakamura, Shinobu Sato, Keisuke Yokoyama, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Histochemistry and cell biology 146 (3) 351 - 62 0948-6143 2016/09 [Refereed][Not invited]
   

  The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.
• Hydrogen sulfide activates TRPA1 and releases 5-HT from epithelioid cells of the chicken thoracic aorta.

  Dugar Delgermurun, Soichiro Yamaguchi, Osamu Ichii, Yasuhiro Kon, Shigeo Ito, Ken-Ichi Otsuguro

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 187 43 - 9 1532-0456 2016/09 [Refereed][Not invited]
   

  Epithelioid cells in the chicken thoracic aorta are chemoreceptor cells that release 5-HT in response to hypoxia. It is likely that these cells play a role in chemoreception similar to that of glomus cells in the carotid bodies of mammals. Recently, H2S was reported to be a key mediator of carotid glomus cell responses to hypoxia. The aim of the present study was to reveal the mechanism of action of H2S on 5-HT outflow from chemoreceptor cells in the chicken thoracic aorta. The 5-HT outflow induced by NaHS, an H2S donor, and Na2S3, a polysulfide, was measured by using a HPLC equipped with an electrochemical detector. NaHS (0.3-3mM) caused a concentration-dependent increase in 5-HT outflow, which was significantly inhibited by the removal of extracellular Ca(2+). 5-HT outflow induced by NaHS (0.3mM) was also significantly inhibited by voltage-dependent L- and N-type Ca(2+) channel blockers and a selective TRPA1 channel blocker. Cinnamaldehyde, a TRPA1 agonist, mimicked the secretory response to H2S. 5-HT outflow induced by Na2S3 (10μM) was also inhibited by the TRPA1 channel blocker. Furthermore, the expression of TRPA1 was localized to 5-HT-containing chemoreceptor cells in the aortic wall. These findings suggest that the activation of TRPA1 and voltage-dependent Ca(2+) channels is involved in H2S-evoked 5-HT release from chemoreceptor cells in the chicken aorta.
• Spatiotemporal distribution of extracellular matrix changes during mouse duodenojejunal flexure formation.

  Sawa Onouchi, Osamu Ichii, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon

  Cell and tissue research 365 (2) 367 - 79 0302-766X 2016/08 [Refereed][Not invited]
   

  Although gut flexures characterize gut morphology, the mechanisms underlying flexure formation remain obscure. Previously, we analyzed the mouse duodenojejunal flexure (DJF) as a model for its formation and reported asymmetric morphologies between the inner and outer bending sides of the fetal mouse DJF, implying their contribution to DJF formation. We now present the extracellular matrix (ECM) as an important factor for gut morphogenesis. We investigate ECM distribution during mouse DJF formation by histological techniques. In the intercellular space of the gut wall, high Alcian-Blue positivity for proteoglycans shifted from the outer to the inner side of the gut wall during DJF formation. Immunopositivity for fibronectin, collagen I, or pan-tenascin was higher at the inner than at the outer side. Collagen IV and laminins localized to the epithelial basement membrane. Beneath the mesothelium at the pre-formation stage, collagen IV and laminin immunopositivity showed inverse results, corresponding to the different cellular characteristics at this site. At the post-formation stage, however, laminin positivity beneath the mesothelium was the reverse of that observed during the pre-formation stage. High immunopositivity for collagen IV and laminins at the inner gut wall mesenchyme of the post-formation DJF implied a different blood vessel distribution. We conclude that ECM distribution changes spatiotemporally during mouse DJF formation, indicating ECM association with the establishment of asymmetric morphologies during this process.
• MRL/MpJ mice show unique pathological features after experimental kidney injury.

  Daichi Shiozuru, Osamu Ichii, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Yasuhiro Kon

  Histology and histopathology 31 (2) 189 - 204 0213-3911 2016/02 [Refereed][Not invited]
   

  Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.
• Comparative analysis of mediastinal fat-associated lymphoid cluster development and lung cellular infiltration in murine autoimmune disease models and the corresponding normal control strains.

  Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon

  Immunology 147 (1) 30 - 40 0019-2805 2016/01 [Refereed][Not invited]
   

  We previously discovered mediastinal fat-associated lymphoid clusters (MFALCs) as novel lymphoid clusters associated with mediastinal fat tissue in healthy mice. However, no data about their morphology in immune-associated disease conditions, and their relationship with lung infiltration, is available to date. In the present study, we compared the morphological features of MFALCs in 4-month-old male murine autoimmune disease models (MRL/MpJ-lpr mice and BXSB/MpJ-Yaa mice) with those of the corresponding control strains (MRL/MpJ and BXSB/MpJ, respectively). In addition, we analysed their correlation with lung infiltration. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1 and BrdU was performed to detect T cells and B cells, macrophages, granulocytes and proliferating cells, respectively. The spleen weight to body weight ratios and anti-double-stranded DNA autoantibody titres were found to be significantly higher in the autoimmune models than in the control strains. Furthermore, the autoimmune model presented prominent MFALCs, with a significantly greater ratio of lymphoid cluster area to total mediastinal fat tissue area, and more apparent diffused cellular infiltration into the lung lobes than the other studied strains. Higher numbers of T and B cells, macrophages and proliferating cells, but fewer granulocytes, were observed in the autoimmune models than in the control strains. Interestingly, a significant positive Pearson's correlation between the size of the MFALCs and the density of CD3-, B220- and Iba1-positive cells in the lung was observed. Therefore, our data suggest a potentially important role for MFALCs in the progression of lung disease. However, further investigation is required to clarify the pathological role of MFALCs in lung disease, especially in inflammatory disorders.
• Genetic factors derived from the MRL/MpJ mouse function to maintain the integrity of spermatogenesis after heat exposure.

  M Chihara, T Nakamura, S Otsuka-Kanazawa, O Ichii, Y H A Elewa, Y Kon

  Andrology 3 (5) 991 - 9 2047-2919 2015/09 [Refereed][Not invited]
   

  MRL/MpJ mice possess highly heat-shock-resistant spermatocytes (HRS) in comparison with C57BL/6 mice. This resistance depends on the MRL/MpJ-type loci at the 81 cM region of Chromosome (Chr) 1 and the 40 cM region of Chr 11. To evaluate the functions of these loci in detail, we examined the histopathological changes resulting from experimental cryptorchidism or transient scrotal heat stress (SHS) in the testes of C57BL/6-based congenic strains (B6.MRLc1, B6.MRLc11, and B6.MRLc1c11) carrying the MRL/MpJ-derived loci responsible for HRS. Among cryptorchid testes from congenic strains, those in B6.MRLc1c11 mice showed the highest heat resistance, indicating that the genetic interactions between MRL/MpJ-derived HRS loci on Chrs 1 and 11 may be important for maintaining spermatogenesis under continuous testicular hyperthermia. In contrast, immediately after SHS induction, germ cell loss via apoptosis was inhibited in B6.MRLc11 and B6.MRLc1c11 mice, similar to that in MRL/MpJ mice. However, this HRS phenotype was not observed in C57BL/6 or B6.MRLc1 mice after SHS induction. Furthermore, testicular calcification owing to long-term damage by SHS induction was inhibited in all congenic strains in comparison with that in C57BL/6 mice, indicating that each MRL/MpJ-derived locus on Chrs 1 and 11 acted independently to facilitate the recovery of heat-induced testicular damage by inhibiting calcification. B6.MRLc11 and B6.MRLc1c11 mice showed greater recovery in spermatogenesis than B6.MRLc1 mice 60 days after SHS induction. Therefore, the MRL/MpJ-derived HRS locus on Chr 11 might play an important role in recovery from heat stress damage. On the basis of these results, we concluded that MRL/MpJ-derived loci on Chrs 1 and 11 cooperatively or independently regulate testicular heat sensitivity depending on the various heat stresses.
• Testicular oocytes in MRL/MpJ mice possess similar morphological, genetic, and functional characteristics to ovarian oocytes.

  Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon

  Mechanisms of development 137 23 - 32 0925-4773 2015/08 [Refereed][Not invited]
   

  In general, mammalian males produce only spermatozoa in their testes and females produce only oocytes in their ovaries. However, newborn MRL/MpJ male mice produce oocytes within their testes. In this study, we examined the initiation and progression of oogenesis in fetal and neonatal MRL/MpJ mouse testes and evaluated the characteristics of testicular oocytes. Germ cells with positive reactions to oogenesis markers such as NOBOX oogenesis homeobox and synaptonemal complex protein 3 were observed in the MRL/MpJ fetal testes on embryonic day 18.5. These fetal testicular oocytes possessed maternal-specific methylation patterns of histone and DNA. The level of DNA methylation was still low in postnatal testicular oocytes at day 14 after birth. Additionally, the postnatal testicular oocytes contained both X and Y chromosomes and had the ability to fuse with sperm. These results suggest that some XY germ cells in fetal testes of MRL/MpJ mice enter meiosis prematurely, undergo oogenesis, and differentiate into oocytes. In addition, MRL/MpJ testicular oocytes have the ability to carry on oogenesis before and shortly after birth until they obtain some of the morphological, epigenetic, and functional characteristics of oocytes.
• Asymmetric morphology of the cells comprising the inner and outer bending sides of the murine duodenojejunal flexure.

  Sawa Onouchi, Osamu Ichii, Saori Otsuka-Kanazawa, Yasuhiro Kon

  Cell and tissue research 360 (2) 273 - 85 0302-766X 2015/05 [Refereed][Not invited]
   

  The asymmetric shape of component cells determines the asymmetric features of developing organs. Here, we focused on the murine duodenojejunal flexure (DJF), which bends without affecting the mesentery, and analyzed the morphological asymmetries of the mucosal epithelium and gut wall cells between the inner and outer bending sides at embryonic days 10.75-11.75. In the mucosal epithelium, the cell shape and the expression of epithelial markers (Cdx2, E-cadherin) showed no differences between the two DJF sides. In contrast, the gut wall cells comprising the inner and outer sides of the DJF were elongated along the inner-outer axis and perpendicular to this axis, respectively. Furthermore, the gut wall cells in the outer side possessed cytoplasmic processes connecting cells via adherens junctions, but those in the inner side were attached via adherens junctions of juxtaposed cell bodies and were relatively more crowded. In immunohistochemistry experiments, there was no remarkable difference in the positive reactions of markers for mesenchyme (vimentin), smooth muscle cells (αSMA), endothelial cells (LYVE-1, CD34), and undifferentiated neurons (Sox10) between the DJF sides. Interestingly, Tuj1-positive cells, indicating differentiated neurons, were observed in the middle layer of the gut wall, and these cells were significantly more abundant and tended to be larger in the inner side than in the outer side of the DJF. In conclusion, we clarified the asymmetries of gut wall cell morphology and neural differentiation between the inner and outer sides of the DJF. These characteristics of the developing murine DJF indicate its asymmetric formation.
• Morphological characteristics observed during early follicular development in perinatal MRL/MpJ mice.

  Yuma Yamashita, Teppei Nakamura, Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon

  The Japanese journal of veterinary research 63 (1) 25 - 36 0047-1917 2015/02 [Refereed][Not invited]
   

  In perinatal mice, the ovary undergoes drastic morphological changes, as clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. We studied perinatal oocyte development in MRL/MpJ mice, and compared it to that observed in C57BL/6 mice between embryonic day 18.5 and postnatal day 4. Throughout the observation period, compared to C57BL/6 mice, MRL/MpJ mice displayed significantly fewer oocytes in their ovaries. Morphologically, there were no clear differences between the strains at embryonic day 18.5. However, the beginning of folliculogenesis, as evidenced by the expression of NOBOX oogenesis homeobox (Nobox) transcript and protein, was more enhanced in MRL/MpJ mice than in C57BL/6 mice at embryonic day 18.5 and postnatal day 0. In addition, developed follicles were more frequently observed in MRL/MpJ mice than in C57BL/6 mice between postnatal days 0 and 4. In conclusion, the oocyte development during nest breakdown and folliculogenesis was accelerated in MRL/MpJ mice when compared to that observed in C57BL/6 mice.
• MRL/MpJ-Fas(lpr) mice show abnormalities in ovarian function and morphology with the progression of autoimmune disease.

  Yuki Otani, Osamu Ichii, Saori Otsuka-Kanazawa, Masataka Chihara, Teppei Nakamura, Yasuhiro Kon

  Autoimmunity 48 (6) 402 - 11 0891-6934 2015 [Refereed][Not invited]
   

  The immune system is known to affect reproductive function, and maternal-fetal immune tolerance is essential for a successful pregnancy. To investigate the relationship between autoimmune disease and female reproductive function, we performed a comparative analysis of the ovarian phenotypes for C57BL/6 mice, autoimmune disease-prone MRL/MpJ (MRL/+) mice and congenic MRL/MpJ-Fas(lpr) (MRL/lpr) mice harboring a mutation in the Fas gene that speeds disease onset. Both MRL-background strains showed earlier vaginal opening than C57BL/6 mice. The estrous cycle became irregular by 6 and 12 months of age in MRL/lpr mice and mice of the other two strains, respectively. Histological analysis at 3 months revealed that the number of primordial follicles was smaller in MRL-background mice than in C57BL/6 mice after 3 months. In addition, MRL/lpr and MRL/+ mice displayed lower numbers of ovarian follicles and corpora lutea at 3 and 6 months, and 6 and 12 months, respectively, than that in age-matched C57BL/6 mice. MRL/lpr and MRL/+ mice developed ovarian interstitial glands after 3 and 6 months, respectively. In particular, MRL/lpr mice showed numerous infiltrating lymphocytes within the ovarian interstitia, and partially stratified ovarian surface epithelia with more developed microvilli than that observed in C57BL/6 mice at 6 months. No significant differences in serum hormone levels were observed between the strains. In conclusion, MRL/lpr mice display altered ovarian development, morphology and function consistent with the progression of severe autoimmune disease, as these findings are less severe in MRL/+ counterparts.
• Decrease in an Inwardly Rectifying Potassium Conductance in Mouse Mammary Secretory Cells after Forced Weaning.

  Akihiro Kamikawa, Shota Sugimoto, Osamu Ichii, Daisuke Kondoh

  PloS one 10 (10) e0141131  1932-6203 2015 [Refereed][Not invited]
   

  Mammary glands are physiologically active in female mammals only during nursing. Immediately after weaning, most lactation-related genes are downregulated and milk production ceases. In our previous study, we have detected an inwardly rectifying potassium channel (Kir) 2.1-like current in mammary secretory (MS) cells freshly isolated from lactating mice. This current is highly sensitive to external Ba2+. The potassium permeability of the Kir channels may contribute to the secretion and/or preservation of ions in milk. We hypothesized that the functions of the Kir channels in MS cells are regulated after weaning. To test this hypothesis, we examined the effect of forced weaning on the Ba2+-sensitive Kir current and Kir2.1 expression in the mouse mammary glands. Twenty-four hours after weaning, the lumina of mammary acini were histologically enlarged by milk accumulation. The whole-cell patch-clamp analyses showed that the Ba2+-sensitive Kir current in the post-weaning MS cells was smaller than in the lactating MS cells. The inward conductances of the current in the lactating and post-weaning cells were 4.25 ± 0.77 and 0.93 ± 0.34 nS, respectively. Furthermore, real-time PCR and Western blot analyses showed that Kir2.1 mRNA and protein expression decreased in the post-weaning mammary gland (mRNA, 90% reduction; protein, 47% reduction). Moreover, the local milk accumulation caused by teat sealing decreased Kir conductance in MS cells (2.74 ± 0.45 and 0.36 ± 0.27 nS for control and sealed mammary glands, respectively). This was concomitant with the reduction in the Kir2.1 mRNA expression. Our results suggest that milk stasis after weaning immediately decreases the Kir conductance in MS cells. This decrease in the Kir conductance may be partly caused by the reduction in the Kir2.1 mRNA and protein expression. These alterations during the post-weaning period may be involved in the cessation of ion secretion and/or preservation in the milk.
• Overexpression of Toll-like receptor 8 correlates with the progression of podocyte injury in murine autoimmune glomerulonephritis.

  Junpei Kimura, Osamu Ichii, Kosuke Miyazono, Teppei Nakamura, Taro Horino, Saori Otsuka-Kanazawa, Yasuhiro Kon

  Scientific reports 4 7290 - 7290 2045-2322 2014/12/03 [Refereed][Not invited]
   

  Members of the Toll-like receptor (TLR) family serve as pathogen sensors and participate in local autoimmune responses. This study found a correlation between glomerular injury and TLR expression by analysing BXSB/MpJ-Yaa (BXSB-Yaa) lupus model mice. In isolated glomeruli, the mRNA expression of several TLRs was higher in BXSB-Yaa mice than in healthy control BXSB mice. In particular, the expression of Tlr8 and its downstream cytokines was markedly increased. In mouse kidneys, TLR8 protein and mRNA localized to podocytes, and TLR8 protein expression in the glomerulus was higher in BXSB-Yaa mice than in BXSB mice. In BXSB-Yaa mice, the glomerular levels of Tlr8 mRNA negatively correlated with the glomerular levels of podocyte functional markers (Nphs1, Nphs2, and Synpo) and positively correlated with urinary albumin levels. Furthermore, the glomerular and serum levels of miR-21, a putative microRNA ligand of TLR8, were higher in BXSB-Yaa mice than in BXSB mice. The urinary levels of Tlr8 mRNA were also higher in BXSB-Yaa mice than in BXSB mice. In conclusion, the overexpression of TLR8 correlates with the progression of podocyte injury in glomerulonephritis. Thus, altered levels of urinary Tlr8 mRNA might reflect podocyte injury.
• Pathogenetic role of an autoimmune susceptibility locus derived from MRL/MpJ strain chromosome 1 in chronic pancreas inflammation.

  Y Okada, T Nakamura, O Ichii, S Otsuka, Y Kon

  Lupus 23 (11) 1112 - 23 0961-2033 2014/10 [Refereed][Not invited]
   

  We examined the role of Mag, an autoimmune susceptibility locus encoded by the telomeric region of MRL/MpJ mouse chromosome 1, in the pathogenesis of autoimmune exocrinopathy. At nine to 12 months of age, strain-specific differences were observed in the pancreas of the animals. B- and T-cell-containing periductal/perivascular cell infiltrations in the pancreases of MRL/MpJ and B6.MRLc1 congenic C57BL/6-background Mag-carrying strains were more severe than were those of C57BL/6. Pancreatic periductal/perivascular cell infiltration was observed frequently in A/J, AKR/N, B6.MRLc1, C57BL/6, and MRL/MpJ, moderately in DBA/1 and DBA/2, and rarely in BALB/c and C3H/He strains. Females tended to have greater pancreatic periductal/perivascular cell infiltration than males. C57BL/6 mice possessed defined borders between cell infiltrations and acini, but borders were indistinct in MRL/MpJ and B6.MRLc1 mice. We attributed this to the invasion of inflammatory cells between each acinus and the disruption of acinar cells around cell infiltrations in the latter strains. No strain-specific differences were observed in the appearance of fibrotic lesions and high endothelial venules in the cell infiltrates. The levels of serum anti-dsDNA antibodies and amylase, and mRNA expression of tumor necrosis factor-α and Fc gamma receptor III (encoded on Mag) in the pancreases, were elevated in MRL/MpJ- and B6.MRLc1-strain mice relative to C57BL/6. These results emphasized the crucial roles of Mag in the molecular and genetic pathogenesis of autoimmune-mediated pancreatitis.
• Characterization of mouse mediastinal fat-associated lymphoid clusters.

  Yaser Hosny Ali Elewa, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon

  Cell and tissue research 357 (3) 731 - 41 0302-766X 2014/09 [Refereed][Not invited]
   

  The association between adipose tissue and immunity has been established and fat-associated lymphoid clusters (FALCs) are considered as a source of immune cells. We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ (MRL) mice strains, LCs without a fibrous capsule and germinal center were observed in white-colored MFTs extending from the diaphragm to the heart. The number and size of the LCs were larger in 12-month-old mice than in 3-month-old mice in all of the examined strains. Moreover, B6 had an especially large number of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells, rather than CD8+ cytotoxic T-cells and no obvious immune cell population difference was present among the strains. Furthermore, high endothelial venules and lymphatic vessels in the LCs were better developed in B6 mice than in the other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating cells were more abundant in the LCs of B6 mice than in the LCs of the other strains and the number of BrdU+ cells increased with age. This is the first report of LCs in mouse MFTs. We suggest that the mouse genetic background affects LC size and number. We term the LCs "mediastinal fat-associated lymphoid clusters". These clusters can be considered as niches for Th cell production.
• The onset of heat-induced testicular calcification in mice: involvement of the telomeric locus on chromosome 1.

  Masataka Chihara, Teppei Nakamura, Naoki Sakakibara, Saori Otsuka, Osamu Ichii, Yasuhiro Kon

  The American journal of pathology 184 (9) 2480 - 92 0002-9440 2014/09 [Refereed][Not invited]
   

  Spermatocytes of MRL/MpJ mice are more heat resistant than those of C57BL/6 mice in experimental cryptorchidism. This phenotype depends in part on the locus at the 81-cM region of MRL/MpJ-type chromosome 1 (Chr 1). To evaluate the function of this locus, we examined pathological changes in mouse testes resulting from transient scrotal heat stress. Immediately after scrotal heat stress, meiosis progression and blood-testis barrier integrity were preserved in MRL/MpJ but not in C57BL/6 mice, nor in a C57BL/6-based congenic strain carrying the MRL/MpJ-derived Chr 1 locus (B6.MRLc1). Testicular damage was severe in the weeks after scrotal heat stress in all three strains; however, testicular calcification was observed only in C57BL/6 and MRL/MpJ mice (initially as nanocrystals in mitochondria of degenerating germ cells). In testes, expression of gremlin 2, a bone morphogenetic protein antagonist encoded on Chr 1, was markedly higher in B6.MRLc1 than in C57BL/6 or MRL/MpJ mice. Furthermore, gremlin-2 and bone morphogenetic protein 2 mRNA levels in heated testes correlated negatively and positively, respectively, with calcification. Thus, although the MRL/MpJ-derived locus on Chr 1 may play a pivotal role in recovery from heat-induced testicular damage, especially via inhibition of calcification, MRL/MpJ mice have a precipitating factor for testicular calcification and heat shock-resistant factors that reside outside the 81-cM region of Chr 1.
• Structural changes of goat parotid salivary gland: pre- and post-weaning periods.

  Y H A Elewa, O Ichii, S Otsuka, Y Hashimoto, Y Kon

  Anatomia, histologia, embryologia 43 (4) 265 - 72 0340-2096 2014/08 [Refereed][Not invited]
   

  Previously, the structure of the adult goat parotid salivary glands (PGs) was studied. However, little information was elucidated of the juvenile ones. This study aimed to clarify the correlations between the structure of goats' PGs and the nature of food intake among milk-suckling kids (MSKs) and diet-fed goats (DFGs). The secretory endpieces of the goats' PGs are of the pure serous type. The serous cells in MSKs showed apical accumulation of numerous secretory granules (SGs) of smaller size and of more intense positive periodic acid-Schiff reaction. Ultrastructurally, most of the SGs in the DFGs contained peripherally located inclusions that showed dense reaction products for acid phosphatase. In MSKs, the PGs showed less-developed basal infoldings, sparseness of the inter-cellular inter-digitations, fewer inter-cellular canaliculi and microvilli and also less-developed myoepithelial cells with fewer and shorter cytoplasmic processes. In conclusion, the less-developed membrane specializations and myoepithelial cells, as well as the accumulated SGs in the PGs of MSKs, suggest that it secretes less saliva with a little secretory activity than that of DFGs, which may be correlated with the reduced masticatory activity.
• Direct synthesis of benzofuro[2,3-b]pyrroles through a radical addition/[3,3]-sigmatropic rearrangement/cyclization/lactamization cascade.

  Masafumi Ueda, Yuta Ito, Yuki Ichii, Maiko Kakiuchi, Hiroko Shono, Okiko Miyata

  Chemistry (Weinheim an der Bergstrasse, Germany) 20 (22) 6763 - 70 2014/05/26 [Refereed][Not invited]
   

  A straightforward synthetic method for the construction of benzofuro[2,3-b]pyrrol-2-ones by a novel domino reaction through a radical addition/[3,3]-sigmatropic rearrangement/cyclization/lactamization cascade has been developed. The domino reaction of O-phenyl-conjugated oxime ether with an alkyl radical allows the construction of two heterocycles with three stereogenic centers as a result of the formation of two C-C bonds, a C-O bond, and a C-N bond in a single operation, leading to pyrrolidine-fused dihydrobenzofurans, which are not easily accessible by existing synthetic methods. Furthermore, asymmetric synthesis of benzofuro[2,3-b]pyrrol-2-one derivatives through a diastereoselective radical addition reaction to a chiral oxime ether was also developed.
• Tick-borne flaviviruses alter membrane structure and replicate in dendrites of primary mouse neuronal cultures.

  Minato Hirano, Kentaro Yoshii, Mizuki Sakai, Rie Hasebe, Osamu Ichii, Hiroaki Kariwa

  The Journal of general virology 95 (Pt 4) 849 - 861 0022-1317 2014/04 [Refereed][Not invited]
   

  Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, detailed mechanisms of viral replication in the brain and features of viral pathogenesis remain poorly understood. We carried out a comparative analysis of replication of neurotropic flaviviruses: West Nile virus, Japanese encephalitis virus and tick-borne encephalitis virus (TBEV), in primary cultures of mouse brain neurons. All the flaviviruses multiplied well in primary neuronal cultures from the hippocampus, cerebral cortex and cerebellum. The distribution of viral-specific antigen in the neurons varied: TBEV infection induced accumulation of viral antigen in the neuronal dendrites to a greater extent than infection with other viruses. Viral structural proteins, non-structural proteins and dsRNA were detected in regions in which viral antigens accumulated in dendrites after TBEV replication. Replication of a TBEV replicon after infection with virus-like particles of TBEV also induced antigen accumulation, indicating that accumulated viral antigen was the result of viral RNA replication. Furthermore, electron microscopy confirmed that TBEV replication induced characteristic ultrastructural membrane alterations in the neurites: newly formed laminal membrane structures containing virion-like structures. This is the first report describing viral replication in and ultrastructural alterations of neuronal dendrites, which may cause neuronal dysfunction. These findings encourage further work aimed at understanding the molecular mechanisms of viral replication in the brain and the pathogenicity of neurotropic flaviviruses.
• BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa

  J. Kimura, O. Ichii, T. Nakamura, T. Horino, S. Otsuka, Y. Kon

  GENES AND IMMUNITY 15 (3) 182 - 189 1466-4879 2014/04 [Refereed][Not invited]
   

  The autoimmune-prone BXSB/MpJ-Yaa mouse is a model of membranous proliferative glomerulonephritis (MPGN). Severe MPGN has been reported only in male BXSB/MpJ-Yaa mice because of the Y-linked autoimmune accelerator (Yaa) locus. However, we show that female BXSB/MpJ mice develop age-related MPGN without Yaa. Female BXSB/MpJ mice clearly developed MPGN characterized by increased mesangial cells, thickening of the glomerular basement membrane (GBM), double contouring and spike formation of GBM with T-cell infiltrations and podocyte injuries corresponding with increased autoantibody production and albuminuria. Analysis of the renal levels of the Fc gamma receptor (Fcgr) and interferon-activated gene 200 (Ifi200) family genes, which are MPGN candidate genes localized to the telomeric region of chromosome 1 (Chr.1), showed that Fcgr2b levels decreased, whereas Fcgr3 and Ifi202b levels increased in female BXSB/MpJ mice compared with healthy C57BL/6 mice. Furthermore, in isolated glomeruli, microarray analysis revealed that Fcgr3, Fcgr4 and Ifi202b expression was higher in male BXSB/MpJ-Yaa mice than in male BXSB/MpJ mice. These findings indicate that the BXSB/MpJ-type genome causes age-related MPGN with significant contribution from the telomeric region of Chr.1, and Yaa? enhances the expression of genes localizing to this locus, thereby leading to severe MPGN in male mice.
• MicroRNA expression profiling of cat and dog kidneys.

  Osamu Ichii, Saori Otsuka, Hiroshi Ohta, Akira Yabuki, Taro Horino, Yasuhiro Kon

  Research in veterinary science 96 (2) 299 - 303 0034-5288 2014/04 [Refereed][Not invited]
   

  MicroRNAs (miRNAs) play a role in the pathogenesis of certain diseases and may serve as biomarkers. Here, we present the first analysis of miRNA expression in the kidneys of healthy cats and dogs. Kidneys were divided into renal cortex (CO) and medulla (MD), and RNA sequence analysis was performed using the mouse genome as a reference. A total of 277, 276, 295, and 297 miRNAs were detected in cat CO, cat MD, dog CO, and dog MD, respectively. By comparing the expression ratio of CO to MD, we identified highly expressed miRNAs in each tissue as follows: 41 miRNAs including miR-192-5p in cat CO; 45 miRNAs including miR-323-3p in dog CO; 78 miRNAs including miR-20a-5p in cat MD; and 11 miRNAs including miR-132-5p in dog MD. Further, the target mRNAs of these miRNAs were identified. These data provide veterinary medicine critical information regarding renal miRNA expression.
• Genomic analysis of the appearance of ovarian mast cells in neonatal MRL/MpJ mice.

  Teppei Nakamura, Yuko Sakata, Saori Otsuka-Kanazawa, Osamu Ichii, Masataka Chihara, Ken-ichi Nagasaki, Yuka Namiki, Yasuhiro Kon

  PloS one 9 (6) e100617  1932-6203 2014 [Refereed][Not invited]
   

  In MRL/MpJ mice, ovarian mast cells (OMCs) are more abundant than in other mouse strains, and tend to distribute beneath the ovarian surface epithelium at birth. This study investigated the factors regulating the appearance of neonatal OMCs in progeny of the cross between MRL/MpJ and C57BL/6N strains. F1 neonates had less than half the number of OMCs than MRL/MpJ. Interestingly, MRLB6F1 had more neonatal OMCs than B6MRLF1, although they were distributed over comparable areas. Furthermore, in MRL/MpJ fetuses for which parturition was delayed until embryonic day 21.5, the number of OMCs was significantly higher than in age-matched controls at postnatal day 2. These results suggest that the number of OMCs was influenced by the environmental factors during pregnancy. Quantitative trait locus analysis using N2 backcross progeny revealed two significant loci on chromosome 8: D8Mit343-D8Mit312 for the number of OMCs and D8Mit86-D8Mit89 for their distribution, designated as mast cell in the ovary of MRL/MpJ 1 (mcom1) and mcom2, respectively. Among MC migration-associated genes, ovarian expression of chemokine (C-C motif) ligand 17 at mcom1 locus was significantly higher in MRL/MpJ than in C57BL/6N, and positively correlated with the expression of OMC marker genes. These results indicate that the appearance of neonatal OMCs in MRL/MpJ is controlled by environmental factors and filial genetic factors, and that the abundance and distribution of OMCs are regulated by independent filial genetic elements.
• Podocyte injury caused by indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand.

  Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Masaaki Ueno, Yasuhiro Kon, Weiping Chen, Avi Z Rosenberg, Jeffrey B Kopp

  PloS one 9 (9) e108448  1932-6203 2014 [Refereed][Not invited]
   

  Indoxyl sulfate is a uremic toxin and a ligand of the aryl-hydrocarbon receptor (AhR), a transcriptional regulator. Elevated serum indoxyl sulfate levels may contribute to progressive kidney disease and associated vascular disease. We asked whether indoxyl sulfate injures podocytes in vivo and in vitro. Mice exposed to indoxyl sulfate for 8 w exhibited prominent tubulointerstitial lesions with vascular damage. Indoxyl sulfate-exposed mice with microalbuminuria showed ischemic changes, while more severely affected mice showed increased mesangial matrix, segmental solidification, and mesangiolysis. In normal mouse kidneys, AhR was predominantly localized to the podocyte nuclei. In mice exposed to indoxyl sulfate for 2 h, isolated glomeruli manifested increased Cyp1a1 expression, indicating AhR activation. After 8 w of indoxyl sulfate, podocytes showed foot process effacement, cytoplasmic vacuoles, and a focal granular and wrinkled pattern of podocin and synaptopodin expression. Furthermore, vimentin and AhR expression in the glomerulus was increased in the indoxyl sulfate-exposed glomeruli compared to controls. Glomerular expression of characteristic podocyte mRNAs was decreased, including Actn4, Cd2ap, Myh9, Nphs1, Nphs2, Podxl, Synpo, and Wt1. In vitro, immortalized-mouse podocytes exhibited AhR nuclear translocation beginning 30 min after 1 mM indoxyl sulfate exposure, and there was increased phospho-Rac1/Cdc42 at 2 h. After exposure to indoxyl sulfate for 24 h, mouse podocytes exhibited a pro-inflammatory phenotype, perturbed actin cytoskeleton, decreased expression of podocyte-specific genes, and decreased cell viability. In immortalized human podocytes, indoxyl sulfate treatment caused cell injury, decreased mRNA expression of podocyte-specific proteins, as well as integrins, collagens, cytoskeletal proteins, and bone morphogenetic proteins, and increased cytokine and chemokine expression. We propose that basal levels of AhR activity regulate podocyte function under normal conditions, and that increased activation of podocyte AhR by indoxyl sulfate contributes to progressive glomerular injury.
• Decreased miR-26a expression correlates with the progression of podocyte injury in autoimmune glomerulonephritis.

  Osamu Ichii, Saori Otsuka-Kanazawa, Taro Horino, Junpei Kimura, Teppei Nakamura, Manabu Matsumoto, Makoto Toi, Yasuhiro Kon

  PloS one 9 (10) e110383  1932-6203 2014 [Refereed][Not invited]
   

  MicroRNAs contribute to the pathogenesis of certain diseases and may serve as biomarkers. We analyzed glomerular microRNA expression in B6.MRLc1, which serve as a mouse model of autoimmune glomerulonephritis. We found that miR-26a was the most abundantly expressed microRNA in the glomerulus of normal C57BL/6 and that its glomerular expression in B6.MRLc1 was significantly lower than that in C57BL/6. In mouse kidneys, podocytes mainly expressed miR-26a, and glomerular miR-26a expression in B6.MRLc1 mice correlated negatively with the urinary albumin levels and podocyte-specific gene expression. Puromycin-induced injury of immortalized mouse podocytes decreased miR-26a expression, perturbed the actin cytoskeleton, and increased the release of exosomes containing miR-26a. Although miR-26a expression increased with differentiation of immortalized mouse podocytes, silencing miR-26a decreased the expression of genes associated with the podocyte differentiation and formation of the cytoskeleton. In particular, the levels of vimentin and actin significantly decreased. In patients with lupus nephritis and IgA nephropathy, glomerular miR-26a levels were significantly lower than those of healthy controls. In B6.MRLc1 and patients with lupus nephritis, miR-26a levels in urinary exosomes were significantly higher compared with those for the respective healthy control. These data indicate that miR-26a regulates podocyte differentiation and cytoskeletal integrity, and its altered levels in glomerulus and urine may serve as a marker of injured podocytes in autoimmune glomerulonephritis.
• Vitamin A deprivation affects the progression of the spermatogenic wave and initial formation of the blood-testis barrier, resulting in irreversible testicular degeneration in mice.

  Masataka Chihara, Saori Otsuka, Osamu Ichii, Yasuhiro Kon

  The Journal of reproduction and development 59 (6) 525 - 35 0916-8818 2013/12/17 [Refereed][Not invited]
   

  The blood testis-barrier (BTB) is essential for maintaining homeostasis in the seminiferous epithelium. Although many studies have reported that vitamin A (VA) is required for the maintenance of spermatogenesis, the relationships between the BTB, spermatogenesis and VA have not been elucidated. In this study, we analyzed BTB assembly and spermatogenesis in the testes of mice fed the VA-deficient (VAD) diet from the prepubertal period to adulthood. During the prepubertal period, no changes were observed in the initiation and progression of the first spermatogenic wave in mice fed the VAD diet. However, the numbers of preleptotene/leptotene spermatocytes derived from the second spermatogenic wave onwards were decreased, and initial BTB formation was also delayed, as evidenced by the decreased expression of mRNAs encoding BTB components and VA signaling molecules. From 60 days postpartum, mice fed the VAD diet exhibited apoptosis of germ cells, arrest of meiosis, disruption of the BTB, and dramatically decreased testis size. Furthermore, vacuolization and calcification were observed in the seminiferous epithelium of adult mice fed the VAD diet. Re-initiation of spermatogenesis by VA replenishment in adult mice fed the VAD diet rescued BTB assembly after when the second spermatogenic wave initiated from the arrested spermatogonia reached the preleptotene/leptotene spermatocytes. These results suggested that BTB integrity was regulated by VA metabolism with meiotic progression and that the impermeable BTB was required for persistent spermatogenesis rather than meiotic initiation. In conclusion, consumption of the VAD diet led to critical defects in spermatogenesis progression and altered the dynamics of BTB assembly.
• BXSB/MpJ-Yaa mice develop autoimmune dacryoadenitis with the appearance of inflammatory cell marker messenger RNAs in the lacrimal fluid.

  Keigo Kosenda, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon

  Clinical & experimental ophthalmology 41 (8) 788 - 97 1442-6404 2013/11 [Refereed][Not invited]
   

  BACKGROUND: Dacryoadenitis is characteristic of an autoimmune exocrinopathy, e.g. Sjögren syndrome. We pathologically examined the lacrimal glands of autoimmune-prone BXSB/MpJ-Yaa mice for the appearance of pathological signs of dacryoadenitis progression in autoimmune dacryoadenitis models, particularly focusing on messenger RNAs in the lacrimal fluid. METHODS: The lacrimal glands of the BXSB/MpJ-Yaa and C57BL/6 mice were histopathologically analyzed in parallel with the evaluation of lacrimation and messenger RNA expression of water channels (Aqp3, Aqp4 and Aqp5). In addition, autoimmune model mice (MRL/MpJ-lpr/lpr and NZB/NZWF1) were used for evaluating cell infiltration and detecting inflammatory cell marker messenger RNAs (Cd68, Ptprc and Cd3e) in the lacrimal fluids by polymerase chain reaction-based methods. RESULTS: B-cell predominant lymphocytic infiltrations and the destruction of acini were observed in the lacrimal glands of BXSB/MpJ-Yaa mice. There was no significant difference in the quantity of lacrimal fluid between the BXSB/MpJ-Yaa and C57BL/6 mice. In the BXSB/MpJ-Yaa mice, Aqp3 expression increased significantly with the cell infiltration score, whereas expression of Aqp4 and Aqp5 tended to decrease. Aqp3 expression increased significantly with the cell infiltration score in BXSB/MpJ-Yaa mice. Among inflammatory cell markers, Cd68 was more frequently detected in the lacrimal fluid of the BXSB/MpJ-Yaa, MRL/MpJ-lpr/lpr and NZB/NZWF1 mice than in that of the C57BL/6 mice. CONCLUSION: BXSB/MpJ-Yaa mice clearly developed autoimmune dacryoadenitis. The altered expression of water channels in lacrimal glands might be associated with the preservation of lacrimal fluid excretion in BXSB/MpJ-Yaa mice. The detection of inflammatory cell markers in lacrimal fluid could be used as a diagnostic marker for autoimmune dacryoadenitis.
• Analysis of duodenojejunal flexure formation in mice: implications for understanding the genetic basis for gastrointestinal morphology in mammals.

  Sawa Onouchi, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon

  Journal of anatomy 223 (4) 385 - 98 0021-8782 2013/10 [Refereed][Not invited]
   

  The mammalian gut undergoes morphological changes during development. We studied the developing mouse duodenojejunal flexure (DJF) to elucidate the mechanism of formation. During embryonic days 10.75-13.75, DJF formation was morphologically classified into three stages: the expansion stage, flexure formation stage, and flexure elongation stage. From the expansion to the flexure formation stages, the DJF wall showed asymmetric morphology and proliferation along the left-right intestinal axis. From the flexure formation to the flexure elongation stage, the DJF started to bend dorsally with counterclockwise rotation along the antero-caudal intestinal axis, indicating that the original right side of the duodenum was rotated towards the dorsal body wall during development of the DJF. The direction of attachment of the dorsal mesentery to the DJF did not correspond to the bending direction of the DJF during flexure formation, and this finding indicated that the dorsal mesentery contributed very little to DJF formation. During DJF formation, Aldh1a2 and hedgehog mRNAs were detected at the DJF, and their expression levels differed along the bending axis. In conclusion, DJF formation might be triggered by asymmetric morphology and proliferation along the left-right intestinal axis under the control of retinoic acid and hedgehog signaling.
• Mice stage-specific claudin 3 expression regulates progression of meiosis in early stage spermatocytes.

  Masataka Chihara, Ryoyo Ikebuchi, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Atsushi Suzuki, Yumiko Saga, Yasuhiro Kon

  Biology of reproduction 89 (1) 3 - 3 0006-3363 2013/07 [Refereed][Not invited]
   

  Claudin 3 is a protein component of the tight junction strands. Tight junctions between adjacent Sertoli cells form the blood-testis barrier (BTB). During spermatogenesis, seminiferous stage-specific expression of claudin 3 is believed to regulate the migration of preleptotene/leptotene spermatocytes across the BTB. Here, we determined the cell types expressing claudin 3 in adult mouse testis and investigated spermatogenesis after testis-specific in vivo knockdown of claudin 3. The results of in situ hybridization revealed that claudin 3 mRNA was predominantly expressed in germ cells near the basal lamina of seminiferous tubules at stages VI-IX. Furthermore, claudin 3 protein was localized not only to the BTB but also to the cell membrane of STRA8-expressing preleptotene/leptotene spermatocytes in the testis of adult ICR.Cg-Tg(Stra8-EGFP)1Ysa/YsaRbrc mice. Although claudin 3 knockdown did not affect BTB integrity, it did cause a partial delay in spermatocyte migration across the BTB. Moreover, claudin 3 knockdown resulted in a prolonged preleptotene phase during spermatogenesis. These data indicate that the seminiferous stage-specific expression and localization of claudin 3 during spermatogenesis regulate the progression of meiosis by promoting germ cell migration across the BTB.
• Analysis of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells associated with cardiac myogenesis in mouse embryo.

  Yuki Naganuma, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon

  The Journal of veterinary medical science 75 (3) 283 - 90 0916-7250 2013 [Refereed][Not invited]
   

  Caspase activation is associated with skeletal muscle differentiation in mouse embryos. We examined the relationship between cardiac myogenesis and cell death using mice hearts at embryonic days (E) 11.5-15.5 and fetal rat heart H9C2 cells. The number of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells increased with fetal age and was much higher than that of single-stranded DNA (ssDNA)- and active caspase-3 (aCasp3)-positive cells. TUNEL and aCasp3 double staining resulted in 3 types of positive cells: TUNEL(+)/aCasp3(+), TUNEL(+)/aCasp3(-) and TUNEL(-)/aCasp3(+). TUNEL(+)/aCasp3(-) cells were the most common but lacked morphological features of apoptosis, such as nuclear condensation or fragmentation. The expression of anti-apoptotic factors increased during E11.5-15.5. Furthermore, TUNEL-positive H9C2 cells without nuclear condensation or fragmentation were observed only in myotubes later in the culture period. In this study, the dynamics of TUNEL-positive cardiomyocyte was inconsistent with the activation of apoptosis cascade, and their morphological feature was clearly different from representative apoptosis. From these findings, we concluded that the increased number of TUNEL-positive cardiomyocyte, having the DNA strand breaks, would be associated with the progression of cardiac myogenesis.
• Close relations between podocyte injuries and membranous proliferative glomerulonephritis in autoimmune murine models.

  Junpei Kimura, Osamu Ichii, Saori Otsuka, Hayato Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon

  American journal of nephrology 38 (1) 27 - 38 0250-8095 2013 [Refereed][Not invited]
   

  BACKGROUND: Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. METHODS: The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa(+) and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. RESULTS: Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl. CONCLUSION: MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN.
• Relationship between numerous mast cells and early follicular development in neonatal MRL/MpJ mouse ovaries.

  Teppei Nakamura, Saori Otsuka, Osamu Ichii, Yuko Sakata, Ken-Ichi Nagasaki, Yoshiharu Hashimoto, Yasuhiro Kon

  PloS one 8 (10) e77246  1932-6203 2013 [Refereed][Not invited]
   

  In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown.
• Genomic analysis of the appearance of testicular oocytes in MRL/MpJ mice.

  Saori Otsuka, Osamu Ichii, Yuka Namiki, Nobuya Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon

  Mammalian genome : official journal of the International Mammalian Genome Society 23 (11-12) 741 - 8 0938-8990 2012/12 [Refereed][Not invited]
   

  Mammals produce sperm or oocytes depending on their sex; however, newborn MRL/MpJ (MRL) male mice produce oocytes within their testes. We previously reported that one of the genes responsible for this phenotype is present on the MRL-type Y chromosome (Y(MRL)), and that multiple genes, probably autosomal, are also required for the development of this phenotype. In this study we focused on the autosomal genes and examined their relationship with this phenotype by analyzing the progeny from crosses between MRL mice and other strains. We first observed the male F1 progeny from the crosses between female A/J, C57BL/6 (B6), BALB/c, C3H/He, or DBA/2 mice and male MRL mice, and two consomic strains, male B6-Y(MRL) and MRL-Y(B6). Testicular oocytes that were morphologically similar to those of MRL mice were detected in all mouse strains except BALBMRLF1; however, the incidence of testicular oocytes was significantly lower than that in MRL mice. The appearance of testicular oocytes in MRL-Y(B6) mice indicates that this phenotype is strongly affected by genomic factors present on autosomes, and that there is at least one other causative gene on the MRL-type autosomes (MRL testicular oocyte production, mtop) other than that on Y(MRL). Furthermore, a quantitative trait locus (QTL) analysis using N2 backcross progeny from crosses between female MRLB6F1 and male MRL mice revealed the presence of susceptibility loci for the appearance of testicular oocytes at 8-17 cM on Chr 15. These findings demonstrate that the appearance of testicular oocytes is regulated by the genetic factors on Chr 15 and on Y(MRL).
• Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus.

  Ayumi Matsuyama-Kato, Shiro Murata, Masayoshi Isezaki, Rika Kano, Sara Takasaki, Osamu Ichii, Satoru Konnai, Kazuhiko Ohashi

  Virology journal 9 94 - 94 1743-422X 2012/05/21 [Refereed][Not invited]
   

  BACKGROUND: An immunoinhibitory receptor, programmed death-1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), are involved in immune evasion mechanisms for several pathogens causing chronic infections and for neoplastic diseases. However, little has been reported for the functions of these molecules in chickens. Thus, in this study, their expressions and roles were analyzed in chickens infected with Marek's disease virus (MDV), which induces immunosuppression in infected chickens. RESULTS: A chicken T cell line, Lee1, which constitutively produces IFN-γ was co-cultured with DF-1 cells, which is a spontaneously immortalized chicken fibroblast cell line, transiently expressing PD-L1, and the IFN-γ expression level was analyzed in the cell line by real-time RT-PCR. The IFN-γ expression was significantly decreased in Lee1 cells co-cultured with DF-1 cells expressing PD-L1. The expression level of PD-1 was increased in chickens at the early cytolytic phase of the MDV infection, while the PD-L1 expression level was increased at the latent phase. In addition, the expression levels of PD-1 and PD-L1 were increased at tumor lesions found in MDV-challenged chickens. The expressions levels of PD-1 and PD-L1 were also increased in the spleens and tumors derived from MDV-infected chickens in the field. CONCLUSIONS: We demonstrated that the chicken PD-1/PD-L1 pathway has immunoinhibitory functions, and PD-1 may be involved in MD pathogenesis at the early cytolytic phase of the MDV infection, whereas PD-L1 could contribute to the establishment and maintenance of MDV latency. We also observed the increased expressions of PD-1 and PD-L1 in tumors from MDV-infected chickens, suggesting that tumor cells transformed by MDV highly express PD-1 and PD-L1 and thereby could evade from immune responses of the host.
• Altered expression of microRNA miR-146a correlates with the development of chronic renal inflammation.

  Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon

  Kidney international 81 (3) 280 - 92 0085-2538 2012/02 [Refereed][Not invited]
   

  MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that act as post-transcriptional regulators of target mRNA. In this study, we sought to identify the microRNA underlying local inflammation in a murine model of chronic kidney disease (CKD). In microarray analysis of kidneys, the expression of miR-146a/b was elevated in B6.MRLc1 CKD mice that spontaneously develop renal inflammation with age. Primary-microRNA analysis found that elevated miR-146a/b expression in the kidneys of B6.MRLc1 mice was mainly derived from miR-146a rather than miR-146b, and this expression increased with the development of CKD. Histopathological scores for glomerular and interstitial lesions, mRNA expression of inflammatory mediators, and macrophage infiltration were significantly higher in B6.MRLc1 than C57BL/6 mice and were positively correlated with miR-146a expression. In situ hybridization and laser microdissection-RT-PCR showed that miR-146a expression in interstitial lesions containing inflammatory cells was higher than in the glomerulus. The increased expression of the inflammatory-associated genes RELA, IRAK1, IL1B, IL10, and CXCLs was noted in miR-146a/b-silenced human monocytes. The amount of miR-146a was higher in urine sediments of B6.MRLc1 than of C57BL/6 mice. Thus, miR-146a expression in the kidneys and its urinary excretion was specifically associated with the development of interstitial lesions and correlated with inflammatory cell infiltration.
• The 129 genetic background affects susceptibility to glomerulosclerosis in tensin2-deficient mice.

  Tomohiro Nishino, Nobuya Sasaki, Ken-Ichi Nagasaki, Osamu Ichii, Yasuhiro Kon, Takashi Agui

  Biomedical research (Tokyo, Japan) 33 (1) 53 - 6 0388-6107 2012/02 [Refereed][Not invited]
   

  The ICGN mouse strain is a glomerulosclerosis (GS) model that shows significant proteinuria, podocyte morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which represent the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously, we demonstrated that GS in ICGN mice can be attributed to the deletion mutation of the tensin2 (Tns2) gene (Tns2(nep)). Further, the C57BL/6J (B6) mouse is resistant to GS caused by this mutation. 129/Sv is also a popular strain; however, its susceptibility to GS has not been defined. Thus, to determine whether 129/Sv is resistant or susceptible to GS, we produced a congenic strain carrying Tns2(nep) on the 129(+Ter)/Sv (129T) background. 129T congenic mice (129T-Tns2(nep)) did not exhibit albuminuria, renal anemia, increases in BUN, or any severe pathological changes until at least 16 weeks of age. These results indicate that 129T is resistant to GS. Although their usage in biomedical studies is already widespread, 129/Sv mice may afford a late-onset and unique strain applicable to kidney disease research.
• A conserved region in the prM protein is a critical determinant in the assembly of flavivirus particles.

  Kentaro Yoshii, Manabu Igarashi, Osamu Ichii, Kana Yokozawa, Kimihito Ito, Hiroaki Kariwa, Ikuo Takashima

  The Journal of general virology 93 (Pt 1) 27 - 38 0022-1317 2012/01 [Refereed][Not invited]
   

  Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum (ER) and are secreted through the vesicle transport pathway, but the details of the molecular mechanism of virion assembly remain largely unknown. In this study, a highly conserved region in the prM protein was identified among flaviviruses. In the subviral particle (SP) system of tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus, secretion of SPs was impaired by a mutation in the conserved region in the prM protein. Viral proteins were sparse in the Golgi complex and accumulated in the ER. Ultrastructural analysis revealed that long filamentous structures, rather than spherical SPs, were observed in the lumen of the ER as a result of the mutation. The production of infectious virions derived from infectious cDNA of TBEV was also reduced by mutations in the conserved region. Molecular modelling analysis suggested that the conserved region is important for the association of prM-envelope protein heterodimers in the formation of a spike of immature virion. These results are the first demonstration that the conserved region in the prM protein is a molecular determinant for the flavivirus assembly process.
• Infection of Hantaan virus strain AA57 leading to pulmonary disease in laboratory mice.

  Takahiro Seto, Noriyo Nagata, Keisuke Yoshikawa, Osamu Ichii, Takahiro Sanada, Ngonda Saasa, Yuka Ozaki, Yasunori Kon, Kentaro Yoshii, Ikuo Takashima, Hiroaki Kariwa

  Virus research 163 (1) 284 - 90 0168-1702 2012/01 [Refereed][Not invited]
   

  Hantaan virus (HTNV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). The pathogenesis of HFRS has not been fully elucidated, mainly due to the lack of a suitable animal model. In laboratory mice, HTNV causes encephalitis. However, that symptom is dissimilar to human hantavirus infections. We found that HTNV strain AA57 (isolated from Apodemus agrarius in Far East Russia) caused pulmonary disease in 2-week-old ICR mice. The clinical signs of the infected mice were piloerection, trembling, hunching, labored breathing, and body-weight loss. A large volume of pleural effusion was collected from thoracic cavities of the dead mice. Overall, 45% of the mice inoculated with 3000 focus forming units (FFU) of the virus began to show clinical symptoms at 8 days post-inoculation, and 25% of the inoculated mice died within 3 days of onset of the disease. The morbidity and mortality rates of the mice inoculated with 30-30,000FFU of HTNV strain AA57 were roughly equivalent. The highest rates of virus positivity (11/12) and the highest titers of HTNV strain AA57 were detected in the lungs of the dead mice, while lower detection rates and viral titers were found in the heart, kidneys, spleen, and brain. Interstitial pneumonia, perivascular edema, hemorrhage, inflammatory infiltration and vascular failure were observed in the lungs of the sick mice. Hantaviral antigens were detected in the lung endothelial cells of the sick mice. The symptoms and pathology of this mouse model resemble those of hantavirus pulmonary syndrome (HPS) and, to a certain extent, those of HFRS. This is the first report that, in laboratory mice, the HFRS-related hantavirus causes a HPS-like disease and shares some symptom similarities with HFRS.
• Ovarian cysts in MRL / MpJ mice are derived from the extraovarian rete: a developmental study.

  Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yaser Hosny Ali Elewa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon

  Journal of anatomy 219 (6) 743 - 55 0021-8782 2011/12 [Refereed][Not invited]
   

  MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
• Pathological correlations between podocyte injuries and renal functions in canine and feline chronic kidney diseases.

  O Ichii, A Yabuki, N Sasaki, S Otsuka, H Ohta, M Yamasaki, M Takiguchi, Y Namiki, Y Hashimoto, D Endoh, Y Kon

  Histology and histopathology 26 (10) 1243 - 55 0213-3911 2011/10 [Refereed][Not invited]
   

  Podocytes cover the glomerulus and their adjacent foot processes form a principal barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this study, we analyzed the correlations between podocyte injuries and renal dysfunctions in domestic carnivores. Dogs and cats were divided into normal and CKD groups according to renal histopathology and plasma creatinine values. Immunostaining results showed that linear reactions of slit diaphragm molecules, e.g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a granular pattern in the CKD group, and their intensities significantly decreased with the number of podocytes in the glomerulus. Moreover, the expression of nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly lower than that in normal animals, and negatively correlated with creatinine. Although no significant correlation between renal dysfunction and podocyte injury was detected in cats, histoplanimetric scores of tubulointerstitial lesions in CKD cats were higher than those in both normal cats and diseased dogs. Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD animals. In conclusion, podocyte injuries such as podocytopenia and decreased expression of nephrin and ACTN4 in the glomerulus were more strongly correlated with renal dysfunction in dogs than in cats. These findings suggest that the CKD pathogenesis, especially susceptibilities to podocyte injuries, differed between dogs and cats.
• Distinctive and critical roles for cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in mice.

  Ayo Yila Simon, Nobuya Sasaki, Osamu Ichii, Kiichi Kajino, Yasuhiro Kon, Takashi Agui

  Microbes and infection 13 (8-9) 783 - 97 1286-4579 2011/08 [Refereed][Not invited]
   

  Respiratory viral infections result in severe pulmonary injury, to which host immune response may be a significant contributor. At present, it is not entirely clear the extent to which lung injury is a necessary consequence of host defense. In this report, we use functional genomics approach to characterize the key roles of cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in resistant C57BL/6J and susceptible DBA/2J mice. Infected mice manifested an immune-inflammatory response characterized by the pulmonary influx of neutrophils and mononuclear cells. DBA/2J mice mounted a vigorous immune response, with significant up-regulation of cytokine/chemokine genes in two successive waves through the course of infection. Whereas, C57BL/6J mice displayed an efficient immune response with less severe pathology and clusters of immune-inflammatory responsive genes were exclusively up-regulated on day 4 in this strain. Overall, DBA/2J mice exhibited a dysregulated hyper-inflammatory cytokine/chemokine cascades that does not limit viral spread resulting in a predisposition to severe lung pathology. This response is similar to severe human respiratory paramyxovirus infections, which will serve as a model for the elucidation of hyper-immune inflammatory response that result to severe immunopathology in respiratory viral infections.
• Identifying a new locus that regulates the development of rete ovarian cysts in MRL/MpJ mice.

  Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Yasuhiro Kon

  The Japanese journal of veterinary research 59 (2-3) 79 - 88 0047-1917 2011/08 [Refereed][Not invited]
   

  MRL/MpJ (MRL) is a mouse model for autoimmune disease and develops ovarian cysts with age. The ovarian cysts originate from the rete ovarii, which is considered to be the remnant of fetal mesonephric tubules. In a previous study, we analyzed the genetic background of ovarian cysts by using backcross progenies between MRL and C57BL/6N (B6) mice. By interval mapping, suggestive linkages were detected on several chromosomes (Chrs), and a significant linkage on Chr 14 was designated as MRL Rete Ovarian Cyst (mroc). In the present study, which evaluated 113 F2 intercross progenies, a significant linkage appeared on Chr 6 at the marker position D6Mit188 (likelihood ratio statistic = 18.5). In particular, the peak regions of Chrs 6 and 14, which contain major causative loci by backcross analysis, showed close reverse interaction. From these results, a locus on Chr 6 was identified as mroc2, the second major locus associated with ovarian cyst formation in MRL mice.
• Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial transition in developing kidneys of C57BL/6 mice.

  Tomonori Kanazawa, Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon

  The Journal of veterinary medical science 73 (5) 601 - 7 0916-7250 2011/05 [Refereed][Not invited]
   

  During kidney development, the metanephric mesenchyme (MM) develops into the nephron through mesenchymal-epithelial transition (MET). We have previously reported that knock-down of the expression of hepatocyte nuclear factor 4 alpha (Hnf4a) gene induces failure of cellular organization in the condensed mesenchyme (CM) of cultured embryonic kidneys. To elucidate the details of MET during nephrogenesis, embryonic mouse kidneys were analyzed by electron microscopy, immunohistochemistry, and molecular biology. The findings showed that the intercellular junction, but not the basal lamina, was present in the CM. Additionally, immediately after Hnf4a gene expression, the expression of epithelial genes (Krt8, Tjp1, and Cdh1) increased, and those of mesenchymal genes (Acta1 and Vim) decreased, in the CM compared to the MM. To clarify the relationship between MET and Hnf4α, the fibroblast cell line with forced expression of Hnf4α protein were analyzed. In this model, it was noted that Hnf4α induced increasing epithelial and decreasing mesenchymal gene expression. In these, up-regulation of Pvrl1, -2, and Mllt4 genes which mediate the formation of apico-basal polarity, were found. These results, and those of previous findings, indicate that Hnf4α protein is associated with the initiation of MET in early nephrogenesis.
• High-resolution linkage mapping of the rat hooded locus.

  Daisuke Torigoe, Osamu Ichii, Ruihua Dang, Takayuki Ohnaka, Shinya Okano, Nobuya Sasaki, Yasuhiro Kon, Takashi Agui

  The Journal of veterinary medical science 73 (5) 707 - 10 0916-7250 2011/05 [Refereed][Not invited]
   

  To identify a gene responsible for the hooded phenotype in the rat, high-resolution linkage mapping for the hooded locus was performed using IS (non-hooded) and LEA (hooded) rats. The map revealed that only Kit gene existed in the critical region, suggesting that the Kit is a strong candidate gene. However, mutation was not found in the coding region of the LEA rat Kit gene. Further, the expressions of Kit mRNA were not different in fetal neural tubes and both neonatal and adult skins between IS and LEA rats. Furthermore, Kit-positive cells, possibly melanocytes, were found in the non-pigmented hair follicles of hooded phenotype rats. Several hypotheses are conceivable to account for mechanisms in the appearance of hooded phenotype.
• Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis.

  Junpei Kimura, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon

  PloS one 6 (1) e16472  1932-6203 2011/01/31 [Refereed][Not invited]
   

  The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.
• Molecular pathology of murine ureteritis causing obstructive uropathy with hydronephrosis.

  Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon

  PloS one 6 (11) e27783  2011 [Refereed][Not invited]
   

  Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents.F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters.We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts.
• Cytoarchitectural differences of myoepithelial cells among goat major salivary glands.

  Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon

  Veterinary research communications 34 (6) 557 - 67 0165-7380 2010/08 [Refereed][Not invited]
   

  Previously, the distribution of myoepithelial cells (mecs) in the salivary glands was studied by both immunohistochemistry, and transmission electron microscopy; however, little was elucidated concerning their morphological features, especially in goats. This study was performed to investigate the correlation between the cytoarchitecture of the mecs in goat major salivary glands (parotid, mandibular, and sublingual glands) and the nature of the saliva secretion. The cytoarchitectural features of the mecs were examined by scanning and transmission electron microscopy as well as immunohistochemically. The secretory endpieces in the parotid gland are of the pure serous type, but in both the mandibular and sublingual glands they are of the mixed type. In all studied glands, the intercalated ducts were covered by mecs which, unlike the large stellate cells that surrounded the secretory endpieces, were spindle-shaped with few cytoplasmic processes. Interestingly, the mecs were found to bulge on the basal surfaces of the serous acini and intercalated ducts in all glands and to be in close contact to the seromucous tubules surface in the mandibular and sublingual glands forming a continuous network around it. In conclusion, the differences in the degree of development of the mecs as well as the number of their cytoplasmic processes may be correlated with the nature of the secretion and the number of the secretory granules. Thus these observations may have some relevance in the diagnosis of atrophy and pathogenic conditions of these glands.
• Structural characteristics of goat (Capra hircus) parotid salivary glands.

  Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shinhyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon

  The Japanese journal of veterinary research 58 (2) 121 - 35 0047-1917 2010/08 [Refereed][Not invited]
   

  The structural characteristics of the parotid glands in small ruminants (goat, sheep) were observed and compared to those of a major laboratory animal, the mouse. Their parotid glands consist of the purely serous type. Ultrastructurally, the serous acini of goats and sheep were characterized by the presence of well-developed basolateral expansions of folds, which are characteristics of electrolyte- and water-transporting epithelium. Moreover in ruminants, unlike the mouse, the presence of numerous intercellular canaliculi as well as microvilli projecting into both the intercellular canaliculi and the lumina of the serous acini provided a large surface area for osmotic equilibrium and isotonic saliva secretion. Most of the secretory granules in goats and sheep contained peripherally located inclusions that showed dense reaction products for acid phosphatase. This indicates that most of the secretory granules undergo lysosomal degradation rather than secretion. An apocrine mode of secretion of some secretory granules was occasionally observed in some acini of goats and sheep but only exocytotic features were observed in mice. In the goat, the serous acini showed three morphologically different types, which might be an indication of different activity phases. Furthermore, alpha-smooth muscle actin-, and vimentin-positive myoepithelial cells were observed only around the serous acini and the intercalated ducts. From these findings, we consider that the structural characteristics of ruminant parotid glands might reflect their physiological role in the copious isotonic saliva secretion with a low protein concentration.
• Overexpression of interferon-activated gene 202 (Ifi202) correlates with the progression of autoimmune glomerulonephritis associated with the MRL chromosome 1.

  O Ichii, A Kamikawa, S Otsuka, Y Hashimoto, N Sasaki, D Endoh, Y Kon

  Lupus 19 (8) 897 - 905 0961-2033 2010/07 [Refereed][Not invited]
   

  B6.MRLc1(82-100) congenic mice carrying the telomeric region of lupus-prone MRL chromosome 1 develop autoimmune glomerulonephritis (GN). The GN susceptibility locus of B6.MRLc1(82-100) contains the interferon activated gene 200 (Ifi200) family, which consists of Ifi202, 203, 204, and 205. Recently, Ifi202 was suggested as a candidate gene for murine lupus. In this study, we assessed the association between Ifi200 family and GN in several disease models. We compared the expression of Ifi200 family members in 24 organs between the C57BL/6 and B6.MRLc1(82-100). The expressions of Ifi200 family members differed between strains, and the most dramatic differences appeared in Ifi202 expression. Briefly, in the blood, immune organs, lungs, and testes mRNA expression was higher in B6.MRLc1(82-100) mice. In the kidney and immune organs, only Ifi202 expression increased with the development of GN in B6.MRLc1(82-100), and significant differences from C57BL/6 were observed even before disease onset. Ifi202 expression in the kidneys of BXSB, NZB/WF1, and MRL/lpr was also significantly high in the early- and late-disease stages. Furthermore, laser microdissection-reverse-transcriptase-polymerase chain reaction analysis confirmed the high Ifi202 expression in all areas of B6.MRLc1(82-100) kidneys. In conclusion, in the Ifi200 family, Ifi202 expressions in the kidney and immune organs significantly increased with GN progression.
• Molecular dynamics of the blood-testis barrier components during murine spermatogenesis.

  Masataka Chihara, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon

  Molecular reproduction and development 77 (7) 630 - 9 1040-452X 2010/07 [Refereed][Not invited]
   

  The blood-testis barrier (BTB) separates the seminiferous epithelium into the adluminal and basal compartments. During murine spermatogenesis, preleptotene/leptotene spermatocytes migrate from the basal to the adluminal compartment through the BTB during stages VIII-IX. In the present study, we focused on the tight junction (TJ) molecules and analyzed their spatiotemporal expression during the murine seminiferous epithelial cycle. Structural analysis revealed that the principal components of the BTB, for example, claudin-3, claudin-11, occludin, and zonula occludens-1 (ZO-1), were localized at the basal and luminal sides of the preleptotene/leptotene spermatocytes during the migration stages (VIII-IX). Although we detected claudin-11, occludin, and ZO-1 throughout spermatogenesis, claudin-3 was only detected during stages VI-IX. Quantitative PCR using dissected seminiferous tubules from three stages (Early: II-VI, Middle: VII-VIII, Late: IX-I) clarified that the mRNA levels of TJ molecules were not correlated with the histoplanimetrical protein levels during spermatogenesis. Additionally, tubulobulbar complexes, considered to be involved in the internalization of TJ, were observed at the BTB site. Furthermore, a significant reduction in the mRNA levels of genes for the degradation of occludin (Itch) and endocytic recycling (Rab13) were observed during the Late and Middle stages, respectively. Therefore, we hypothesized that the lag between mRNA and protein expression of TJ molecules may be due to posttranslational modulation, for example, tubulobulbar complexes and endocytic recycling processes. In conclusion, these findings indicate that the integrity of the BTB is maintained throughout spermatogenesis, and the stage-specific localization of claudin-3 protein plays an important role in regulating BTB permeability.
• Analysis of factors decreasing testis weight in MRL mice.

  Saori Otsuka, Yuka Namiki, Osamu Ichii, Yoshiharu Hashimoto, Nobuya Sasaki, Daiji Endoh, Yasuhiro Kon

  Mammalian genome : official journal of the International Mammalian Genome Society 21 (3-4) 153 - 61 0938-8990 2010/04 [Refereed][Not invited]
   

  MRL/MpJ (MRL) mouse testes have several unique characteristics, including the appearance of oocytes, the occurrence of metaphase-specific apoptosis of meiotic spermatocytes, and the presence of heat-shock-resistant spermatocytes. In the present study we used chromosomal mapping to determine the genomic background associated with small testis size in MRL mice. We prepared and analyzed C57BL/6-based congenic mice carrying MRL mouse loci. Quantitative trait loci (QTL) analysis revealed susceptibility loci for small testis size at 100 cM on chromosome (Chr) 1 and at around 80 cM on Chr 2. Analysis with B6.MRLc1 and B6.MRLc2 congenic mice and double-congenic mice confirmed the QTL data and showed that low testis weight in MRL mice was caused by germ cell apoptosis. Through histological examinations we found that B6.MRLc1 and B6.MRLc2 mice showed stage-specific apoptosis in their testes, the former at metaphase stage XII and the later at pachytene stage IV. Metaphase-specific apoptosis of spermatocytes occurs due to mutation of the exonuclease 1 (Exo1) gene located at 100 cM on Chr 1. Thus, the mutation of the Exo1 gene is also responsible for low testis weight caused by metaphase-specific apoptosis. In conclusion, testis weight is reduced in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1 and 2.
• Quantitative trait locus analysis of ovarian cysts derived from rete ovarii in MRL/MpJ mice.

  Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon

  Mammalian genome : official journal of the International Mammalian Genome Society 21 (3-4) 162 - 71 0938-8990 2010/04 [Refereed][Not invited]
   

  MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of mesonephric tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 "MRL Rete Ovarian Cysts (mroc)." The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, and 14 interact to result in development of ovarian cysts in MRL mice.
• Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions.

  Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Akira Yabuki, Hiroshi Ohta, Mitsuyoshi Takiguchi, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon

  Laboratory investigation; a journal of technical methods and pathology 90 (3) 459 - 75 0023-6837 2010/03 [Refereed][Not invited]
   

  Identification of factors that exacerbate a disease is important for the development of biomarkers. In this study, we discovered ectopic overexpression of interleukin-1 family, member-6 (IL-1F6) in several murine renal diseases. IL-1F6 participates in cytokine/chemokine production in the epithelium. In PCR array analysis for inflammatory mediators, Il1f6 showed the highest expression in the kidney of the B6.MRLc1 glomerulonephritis model. IL-1F6 was localized in the epithelium from the DCTs to CCDs, which showed tubular dilations or epithelial deciduations. Ultrastructual examination of the epithelial cells revealed that IL-1F6 was localized on the cytoplasmic ribosome, vesicles, and nucleus. In and around these tubules, we found infiltrations of CD3-positive T-cells and nestin- or alpha-smooth-muscle actin-positive mesenchymal cells. Expression of the IL-1F6 protein and Il1f6 mRNA in the kidney was increased by the development of TILs in the B6.MRLc1 model and in lupus (BXSB, NZB/WF1, and MRL/lpr), nephrotic syndrome (ICGN), and streptozotocin-induced diabetic models. IL-1F6 was also detected in the epithelia having squamous or deciduous contours in other organs such as the skin, esophagus, thymus, or uterus. In vitro analysis using M-1 cells from the murine collecting duct revealed that Il1f6 mRNA induction was related to the upregulation of IL-6, TGF-beta receptor-1, and mesenchymal markers and to the downregulation of epithelial markers and changes in the squamous cells of the epithelium. Interestingly, urine Il1f6 mRNA expression was detected earlier than renal dysfunctions in these mouse models. Ectopic overexpression of IL-1F6 in kidneys is associated with TILs and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of TILs.
• Expression of caspase family and muscle- and apoptosis-specific genes during skeletal myogenesis in mouse embryo.

  Teppei Ikeda, Tomonori Kanazawa, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon

  The Journal of veterinary medical science 71 (9) 1161 - 8 0916-7250 2009/09 [Refereed][Not invited]
   

  The caspases (Casps) are a family of cysteine proteases that are known to regulate apoptotic signaling. Apoptosis by activation of Casp is strongly associated with embryonal development and regeneration in many organs, therefore indicating that disorders caused by homozygous mutation in Casp genes can result in embryonic lethality. In the present study, the authors investigated the causative relationship between skeletal myogenesis and the activation of Casps by analyzing their dynamics during mouse embryogenesis. Individual myogenetic tissues were obtained from C57BL/6 mouse embryos aged 12.5-17.5 days post-conception (dpc), and the expression of Casps was analyzed by histochemical and molecular biological methods. Immunoreactions for Casp-3, -9 and -12 were detected first in myoblasts, increasing according to embryonal development, as a result of which myoblasts differentiated into myotube cells. On the other hand, the immunoreaction for ssDNA, which is well-known as an apoptosis marker, was little detected during the skeletal myogenesis. Quantification analysis for Casp mRNA expression by RT-PCR as well as by in situ hybridization showed a peak at 15.5 dpc but a decrease at 17.5 dpc. Similar dynamics were detected for Myod1 mRNA, one of the muscle regulatory factors, but not for Fasl, Bax and Rock1, apoptosis-associated factors during skeletal myogenesis. These results suggest that the activation of Casps in skeletal myogenesis is deeply associated with myoblast differentiation, but not directly related to apoptosis.
• Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice.

  Akihiro Kamikawa, Osamu Ichii, Daisuke Yamaji, Takeshi Imao, Chiharu Suzuki, Yuko Okamatsu-Ogura, Akira Terao, Yasuhiro Kon, Kazuhiro Kimura

  Developmental dynamics : an official publication of the American Association of Anatomists 238 (5) 1092 - 9 1058-8388 2009/05 [Refereed][Not invited]
   

  Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin.
• Onset of autoimmune glomerulonephritis derived from the telomeric region of MRL-chromosome 1 is associated with the male sex hormone in mice.

  O Ichii, A Konno, N Sasaki, D Endoh, Y Hashimoto, Y Kon

  Lupus 18 (6) 491 - 500 0961-2033 2009/05 [Refereed][Not invited]
   

  Female B6.MRLc1(82-100) congenic mice develop more severe autoimmune glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on the pathogenesis of AGN in these mice. One-month-old male and female mice were divided into sham-operated group (SG) and gonadectomized group (GG), and the pathological changes were investigated at 8 months. SG females showed higher spleen and thymus weights, serum total IgG and autoantibody levels, glomerular damage scores and percent IgG- and CD3-positive glomeruli as compared with SG males. Gonadectomy showed more remarkable effects in males than in females. Spleen and thymus weights, urinary albumin excretion, glomerular damage scores, percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen were significantly higher in GG males than in SG males. CD3-positive cells were observed in both the thymic cortex and medulla in all animals except SG males. The expression ratio of active Fc gamma receptor (Fcgr) 3 to inhibitory Fcgr2b in the kidneys, which we have previously demonstrated to have a great impact on pathogenesis in B6.MRLc1(82-100), was significantly higher in GG males than in SG males. These results suggested that the differences in the pathogenesis of AGN are primarily because of the inhibitory roles of the male sex hormones.
• Strain differences of cerebral ventricles in mice: can the MRL/MpJ mouse be a model for hydrocephalus?

  Keisuke Hino, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon

  The Japanese journal of veterinary research 57 (1) 3 - 11 0047-1917 2009/05 [Refereed][Not invited]
   

  Hydrocephalus is an intractable disease characterized by the excessive accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles. There are many cases in both human and animals; however, the cause and mechanism of it's development is not clearly understood. In this study, differences of cerebral ventricles in 5 inbred mice strains (MRL/MpJ, C57BL/6, C3H/He, DBA/2 and BALB/c) were investigated by histological techniques to determine the possibility of a new animal model for hydrocephalus. Our analysis showed that significant differences in the volume and the surface area of lateral ventricles in the 5 inbred strains, with MRL/MpJ mice having the largest lateral, third, aqueduct and fourth ventricles. In addition, when MRL/MpJ mice were compared to BALB/c mice on 0 day after birth, the former already had larger lateral ventricles than the latter. Although there were no significant difference in the ratios of ependymal cell types in MRL/MpJ mice and BALB/c mice, the number and the diameter of lipid droplets in MRL/MpJ mice were, interestingly, smaller than those in BALB/c mice. It is well known that ependymal cells absorb nutritional substances in CSF by endocytosis, suggesting the possibility that their decrease may relate to the larger cerebral ventricles in MRL/MpJ. In conclusion, MRL/ MpJ mice have greater volumes in cerebral ventricles than other strains and may be useful for a model showing high susceptibility to hydrocephalus.
• Altered balance of inhibitory and active Fc gamma receptors in murine autoimmune glomerulonephritis.

  Osamu Ichii, Akihiro Konno, Nobuya Sasaki, Daiji Endoh, Yoshiharu Hashimoto, Yasuhiro Kon

  Kidney international 74 (3) 339 - 47 0085-2538 2008/08 [Refereed][Not invited]
   

  Mag is an MRL-derived glomerulonephritis susceptibility locus that includes the Fcgr2b and Fcgr3 genes encoding the inhibitory Fc gamma receptor IIB (FcgammaRIIB) and active FcgammaRIII, respectively. We measured changes in gene balance in three B6.MRLc1 congenic mouse strains containing the 82-86, 92-100 and 100 cM regions of the MRL chromosome 1. We found that only the strain that has 92-100 (which includes Fcgr loci) developed glomerulonephritis. These congenic mice had splenomegaly, elevated blood urea nitrogen, anti-dsDNA antibodies and higher urinary albumin excretion compared to the parental strain C57BL/6(B6). Prior to the development of glomerulonephritis, large CD3- (T cell) and B220- (B cell) positive areas were identified in the spleens of B6.MRLc1(92-100) mice. Both Fc receptors were found in mesangial and dendritic cells; important sites of immune-complex clearance and antigen presentation. The FcgammaRIII-positive areas were more prominent in the congenic strain. Fcgr2b mRNA was lower in the B6.MRLc1(92-100) kidney and spleen than in those organs of the B6 mice while Fcgr3 expression and the Fcgr3 to Fcgr2b mRNA ratio was higher in the congenic strain kidneys, spleen and thymus than in those of the B6 prior to and at an early stage of glomerulonephritis. We conclude that the imbalance of inhibitory and active Fc gamma receptors influences the pathogenesis of glomerulonephritis.
• Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ.

  O Ichii, A Konno, N Sasaki, D Endoh, Y Hashimoto, Y Kon

  Histology and histopathology 23 (4) 411 - 22 0213-3911 2008/04 [Refereed][Not invited]
   

  In lupus erythematosus-prone mice, including the BXSB, NZW and NZB strains, telomeric regions of chromosome 1 (Chr.1) contain major glomerulonephritis susceptibility loci such as Bxs3, Sle1, and Nba2. To assess whether strain MRL, a model for lupus erythematosus, had glomerulonephritis susceptibility loci on Chr.1, we created B6.MRLc1(82-100) congenic mice carrying MRL/MpJ Chr.1 (82-100 cM) based on the C57BL/6 background and investigated renal pathology. From 6 months of age, B6.MRLc1 (82-100) showed the onset of diseases such as splenomegaly due to proliferation of CD3- or B220-positive cells, glomerular damage, and an increased serum anti-dsDNA antibody concentration, and these were earlier and severer in females. The score for glomerular damage was higher in B6.MRLc1(82-100) mice over 12 months old than in C57BL/6 or even in wild-type MRL/MpJ. Immune-complex depositions were demonstrated on glomerular basement membrane in B6.MRLc1(82-100) by immunohistochemistry and electron microscopy. For the percentage of IgG1-positive glomeruli, B6.MRLc1 (82-100) had significantly higher values than C57BL/6. In evaluations of clinical parameters, serum levels of blood urea nitrogen and the anti-dsDNA antibody in B6.MRLc1(82-100) were significantly higher than those in C57BL/6. In conclusion, B6.MRLc1(82-100) clearly developed autoimmune-mediated glomerulonephritis, and we demonstrated that MRL Chr.1 contained a novel glomerulonephritis susceptibility locus. We named this locus Mag (MRL autoimmune glomerulonephritis) and it provided new insights into the genetic basis and pathogenesis of lupus nephritis.
• Immunohistochemical localization of renin, NO synthase-1, and cyclooxygenase-2 in rodent kidney.

  Osamu Ichii, Akira Yabuki, Toshimichi Ojima, Mitsuharu Matsumoto, Kazuyuki Taniguchi, Shusaku Suzuki

  Histology and histopathology 23 (2) 143 - 50 0213-3911 2008/02 [Refereed][Not invited]
   

  The renin-angiotensin system (RAS) and tubuloglomerular feedback (TGF) are central to the maintenance of blood pressure and body fluid composition. Renin, NO synthase-1 (NOS-1), and cyclooxygenase-2 (COX-2) are key regulators of the RAS and TGF. In the present study, to investigate species-specific differences in the RAS and TGF, we immunohistochemically and morphometrically investigated the localization of renin, NOS-1, and COX-2 in the kidneys of various laboratory rodents and comparing males with females (DBA/2Cr mice, F344/N rats, Syrian hamsters, MON/JmsGbs gerbils and Hartley guinea pigs). In all animals, renin-positive immunoreactions were observed in the vascular walls of afferent arterioles. Renin immunoreactions appeared to be more widely distributed in mice. Mice had a greater number of renin-positive arterioles than other species. NOS-1-positive reactions were detected in the macula densa (MD) of all animals. Mice had the greatest number of NOS-1-positive MD cells. In addition to NOS-1-positive reactions, COX-2-positive reactions were observed in the MD of mice, rats, hamsters and gerbils. Interestingly, guinea pigs had no COX-2-positive MD cells. Rats had the greatest number of COX-2-positive MD cells. In nephron segments excluding the MD, the immunohistochemical localization of NOS-1 and COX-2 differed markedly among not only species but also sexes within the same species. In conclusion, we determined that localization of renin, NOS-1, and COX-2 showed large species- and sex-related differences. These data suggest that the regulation mechanisms of the RAS and TGF via renin, NOS-1, and COX-2 differ among rodents.
• Immunohistochemical localization of ghrelin in rodent kidneys.

  Akira Yabuki, Satoshi Taharaguchi, Osamu Ichii, Masayasu Kojima, Yoshihiro Nishi, Hiroharu Mifune, Ryozo Kamimura, Mitsuharu Matsumoto, Shusaku Suzuki

  Histochemistry and cell biology 126 (2) 231 - 8 0948-6143 2006/08 [Refereed][Not invited]
   

  Ghrelin is a novel peptide hormone, originally identified in the rat and human stomach that plays various important roles. In the present study, we report the intra-renal localization of ghrelin in laboratory rodents. Kidneys from 3 month-old mice, rats and hamsters of both sexes were analyzed by immunohistochemistry. Positive signals were clearly observed in the epithelium of the distal tubules, whereas other segments of the nephron or interstitial cells, including juxtaglomerular cells, showed negative reactions. Pre-embedding immunoelectron microscopy revealed positive signals exclusively on the basolateral membrane in the distal tubular cells and in the collecting ducts. In addition, prepro-ghrelin gene expression was assessed by RT-PCR, and the expected 329-bp prepro-ghrelin mRNA was clearly detected in the kidney. On Western blot analysis, although a specific band for ghrelin (3 kDa) was not detected in the kidney, the expected band for prepro-ghrelin (13 kDa) was clearly detected in both the stomach and the kidney. This paper clarified the intra-renal localization of ghrelin.
• Rodent renal structure differs among species.

  Osamu Ichii, Akira Yabuki, Toshimichi Ojima, Mitsuharu Matsumoto, Shusaku Suzuki

  The Journal of veterinary medical science 68 (5) 439 - 45 0916-7250 2006/05 [Refereed][Not invited]
   

  In the present study, we histologically and morphometrically investigated species differences in renal structure using laboratory rodents (mice, gerbils, hamsters, rats, and guinea pigs). Morphometric parameters were as follows, 1) diameter of the cortical renal corpuscles, 2) diameter of the juxtamedullary renal corpuscles, 3) percentage of the renal corpuscles with a cuboidal parietal layer, 4) number of nuclei in proximal convoluted tubules (PCTs) per unit area of cortex, 5) semi-quantitative score of the periodic acid-Schiff (PAS) -positive granules in PCTs, and 6) semi-quantitative score of the PAS-positive granules in proximal straight tubules (PSTs). Significant species differences were detected for each parameter, and particularly severe differences were observed in the PAS-positive granules of PCTs and PSTs. Granular scores varied among species and sexes. Vacuolar structures that did not stain with PAS or hematoxylin-eosin were observed in the renal proximal tubules. The appearance and localization of these vacuolar structures differed remarkably between species and sexes.

Books etc

• 新生子MRL/MpJマウスにおいて卵巣マスト細胞は卵巣-卵巣采結合部の方向に遊走する : 局在変化が明らかにするマスト細胞の新たな役割 (特集 マスト細胞研究の新展開)

  中村鉄平, 市居修, Yaser Hosny Ali Elewa, 昆泰寛 
  臨床免疫・アレルギー科、科学評論社 2019
• A possibility of the iBTA tissues derived from animals for off-the-shelf biomaterials

  佐藤康史, 岩井良輔, 西邑隆徳, 市居修, 宮本伸二, 秋吉秀保, 中山泰秀 (Joint work)
  日本人工臓器学会 株式会社秀潤社 2019
• 牛の乳房炎

  日本乳房炎研究会編 (Joint work第3章菌がつくるバイオフィルムとは)
  緑書房 2018/11
• 獣医組織学第7版

  日本獣医解剖学会編 (Contributor第12章「腎臓」、第19章「家禽の組織学」)
  学窓社 2017/03
• カラーアトラス獣医解剖学第2版

  カラーアトラス獣医解剖学編集委員会 (Joint translation第12章「鳥類の解剖学」)
  緑書房 2016/03
• 猫の解剖 カラーリングアトラス

  九郎丸正道監修 (Joint translation「泌尿器」、「呼吸器」)
  学窓社 2014
• 獣医組織学第6版

  日本獣医解剖学会編 (Contributor第12章「腎臓」、第19章「家禽の組織学」)
  学窓社 2014
• 小動物の実践歯科学

  Brool A. Niemiec (Joint translation第1章 解剖学と生理学)
  緑書房 2013/03
• Annual Review 腎臓

  富野康日己ら編 (ContributorC分子生物学 腎臓病のmiRNA解析)
  中外医学社 2013/01
• 獣医解剖・組織・発生学

  日本獣医解剖学会編 (Contributor獣医解剖学 第10章 泌尿器系)
  学窓社 2012/05
• 獣医組織学第5版

  日本獣医解剖学会編 (Contributor第12章「腎臓」)
  学窓社 2011/03

Conference Activities & Talks

• PCBs 曝露によるネコ肝トランスクリプトームへの影響 Effects of PCBs exposure to the feline liver transcriptome

  水川 葉月, Hoa Thanh Ngyuen, 岩田久人, 野見山 桂, 池中良徳, 中山翔太, 横山 望, 市居 修, 滝口満喜, Kraisiri Khidkhan, 田辺信介, 石塚真由美

  第29回環境化学討論会  2020/06
• デカブロモジフェニルエーテル（BDE209）の長期曝露がイエネコへ及ぼす影響 In vivo toxicokinetic analysis of long-term exposure to BDE209 on domestic cat

  田中 啓介, 野見山 桂, 水川 葉月, 髙口 倖暉, 田上 瑠美, 横山 望, 市居 修, 滝口 満喜, 笹岡 一慶, 中山 翔太, 池中 良徳, 石塚 真由美, 国末 達也, 田辺 信介

  第29回環境化学討論会  2020/06
• 走査型顕微鏡の応用的手法による腎病理評価

  市居 修, Md. Abdul Masum, Yaser Hosny Ali Elewa, 昆 泰寛

  日本顕微鏡学会第62回シンポジウム  2019/11
• Possible role of the novel mediastinal fat associated lymphoid clusters in human, animals and poultry respiratory diseases progression

  Y. H. A. Elewa, O. Ichii, T. Nakamura, Y. Kon. The, international scientific conference, faculty of veterinary medicine

  The 4th international scientific conference  2019/10
• 自己免疫疾患モデルマウスにみられる涙液産生組織の形態学的変化

  平石 真也, 市居 修, 中村 鉄平, 難波 貴志, Yaser Hosny Ali Elewa, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• コットンラットの下咽頭梨状窩瘻を構成する細胞の組織化学的特徴

  中村 鉄平, 市居 修, 入江 隆夫, 寸田 祐嗣, 細谷 実里奈, 長崎 健一, Yaser Hosny Ali Elewa, 三嶋 隆, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• 自己免疫疾患モデルマウスで変化する腎臓内 Interleukin 1 family の発現バランス

  難波 貴志, 市居 修, 中村 鉄平, Yaser Hosny Ali Elewa, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• 動物の尿路関連リンパ組織（UTALT）に発現する分子群

  市居 修, 中村 鉄平, 堀野 太郎, 細谷 実里奈, Yaser Hosny Ali Elewa, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• 加齢マウスの尿生殖器における局所リンパ組織の探索

  山下 渚, 市居 修, 大谷 祐紀, Masum Md.Abdul, Yaser Hosny Ali Elewa, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• マウス生体内異物反応の経時観察 ―組織局所の炎症と線維化の関連性―

  大江 紗央, 市居 修, 難波 貴志, 大谷 祐紀, Masum Md. Abdul, 中村 鉄平, Yaser Hosny Ali Elewa, 西邑 隆徳, 中山 泰秀, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• マウスの卵巣嚢－腹腔連絡路（卵巣嚢孔）

  細谷 実里奈, 市居 修, 中村 鉄平, 難波 貴志, Yaser Hosny Ali Elewa, 渡邉 敬文, 植田 弘美, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• Unique morphological characteristics in the ovary of cotton rat（Sigmodon hispidus）

  Md Rashedul Islam, 市居 修, 中村 鉄平, 入江 隆夫, Masum Md Abdul, Yaser Hosny Ali Elewa, 昆 泰寛

  第162回日本獣医学会学術集会  2019/09
• ワクモ由来Adipocyte plasma membrane-associated proteinの抗ワクモワクチン抗原としての評価

  森田 鮎, 竹原 昌生, 村田 史郎, 伊勢崎 政美, 藤澤 宗太郎, 種子野 章, 酒井 英史, 宇野 有紀子, 小川 遼, 市居 修, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦

  第162回日本獣医学会学術集会  2019/09
• 慢性腎臓病の猫の腎臓におけるperoxisome proliferator activated receptor-γの発現動態

  矢吹 映, 上原 由季, 吉田 千紘, 市居 修, 大和 修

  第162回日本獣医学会学術集会  2019/09
• 尿路関連リンパ組織と17型コラーゲンの発現

  市居修, 中村鉄平, 堀野太郎, 細谷実里奈, Yaser Hosny Ali Elewa, 昆泰寛

  第65回東北・北海道連合支部学術集会  2019/09
• Possible role of natural helper cells within the mediastinal fat-associated lymphoid cluster and lung in papain induced lung asthma mouse model

  Yaser Hosny Ali Elewa, 市居修, 中村鉄平, 昆泰寛

  第65回東北・北海道連合支部学術集会  2019/09
• SLC:Wistar/STラットで認めた片側性甲状腺形成不全の解析

  中村鉄平, 市居修, 寸田祐嗣, Yaser Hosny Ali Elewa, 服部秀樹, 長﨑健一, 昆泰寛

  第65回東北・北海道連合支部学術集会  2019/09
• Effect of systemic autoimmune disease on the mouse reproductive function.

  uki Otani, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon

  The 7th Congress of Asian Association of Veterinary Anatomists (Asian AVA)
• Elucidation of the pathogenesis of lung asthma development and recovery: Possible immune cells’ crosstalk within lung and mediastinal fat associated lymphoid clusters in papain induced lung asthma mice model.

  Yaser Hosny Ali Elewa, Osamu, Ichii, Teppei, Nakamura, Yasuhiro, Kon

  The 7th Congress of Asian Association of Veterinary Anatomists (Asian AVA).  2019/09
• Application of virtual slide system to histological education in Hokkaido University.

  Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon

  The 7th Congress of Asian Association of Veterinary Anatomists (Asian AVA).  2019/09
• Unique morphological characteristics in the ovary of cotton rat (Sigmodon hispidus).

  Md. Rashedul Islam, Osamu Ichii, Teppei Nakamura, Takao Irie, Md. Abdul Masum, Yaser Hosny Ali Elewa, Yasuhiro Kon

  The 7th Congress of Asian Association of Veterinary Anatomists (Asian AVA).  2019/09
• Altered bone morpho-function in autoimmune disease-prone mice

  Takashi Namba, Osamu Ichii, Md. Abdul Masum, Yuki Otani, Saori Otsuka-Kanazawa, Yaser Hosny Ali Elewa, Yasuhiro Kon

  The 7th Congress of Asian Association of Veterinary Anatomists (Asian AVA)  2019/09
• 動物の尿生殖器関連リンパ組織

  市居 修, 中村 鉄平, 堀野 太郎, 山下 渚, 細谷 実里奈, Yaser Hosny Ali Elewa, 昆 泰寛

  第12回 日本獣医腎泌尿器学会学術集会  2019/08
• 犬におけるシスプラチン投与による腎傷害と臨床病理学的パラメータの変動

  岡本茉里, 市居 修, 三重慧一郎, 西田英高, 秋吉秀保

  第12回 日本獣医腎泌尿器学会学術集会  2019/08
• iBTA －汎動物学への応用－

  市居 修

  第一回iBTA再生医療研究会  2019/03
• 蛋白尿―糸球体の形態機能とその制御分子から―

  市居修

  第15回日本獣医内科学アカデミー  2019/02
• Innate immunity through Mediastinal fat-associated lymphoid cluster in papain induced lung asthma mice model.

  Yaser Hosny Ali Elewa, Osamu, Ichii, Teppei, Nakamura, Yasuhiro, Kon

  The 42nd Annual Conference of the Egyptian Society of Histology and Cytology.  2018/12
• Effects of PCB exposure on thyroid hormone levels in serum of dogs and cats

  Kohki Takaguchi, Hiroyuki Nishikawa, Hazuki Mizukawa, Rumi Tanoue, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shouta M, M. Nakayama, Yoshinori Ikenaka, Tatsuya Kunisue, Mayumi Ishizuka, Shinsuke Tanabe, Hisato Iwata, d, Kei

  SETAC North America 39th Annual Meeting  2018/11
• iBTA組織のoff-the-shelf人工臓器をめざして：ウシバイオシートの異種移植

  中山泰秀, 大島奈公子, 古越真耶, 巽 英介, 市居 修, 西邑 隆徳

  第56回日本人工臓器学会大会  2018/11
• 生体内組織形成術(iBTA)で生産したウシ由来バイオシートの組織構造と移植適性

  今山 知佳, 鈴木 貴弘, 小林 謙, 三谷 朋弘, 市居 修, 中山 泰秀, 古越 真耶, 池田 哲平, 小千田 圭吾, 西邑 隆徳

  第14回結合組織勉強会  2018/10
• Autoimmune disease alters systemic ciliary function in MRL/MpJ-Faslpr/lpr mice

  細谷実里奈, 市居 修, Yaser Hosny Ali Elewa, 中村鉄平, 昆 泰寛

  The 6th Sapporo Summer Symposium for One Health  2018/09
• Causative molecules to increase the apoptosis of meiotic spermatocytes in autoimmune disease-prone BXSB/MpJ-Yaa mice

  大谷祐紀, 市居 修, Yaser Hosny Ali Elewa, 昆 泰寛

  The 6th Sapporo Summer Symposium for One Health  2018/09
• Overexpression of Toll-like receptor 9 correlates with podocyte injury in murine autoimmune glomerulonephritis

  Md. Abdul Masum, 市居 修, Yaser Hosny Ali Elewa, 中村 鉄平, 大谷 祐紀, 細谷 実里奈, 昆 泰寛

  The 6th Sapporo Summer Symposium for One Health  2018/09
• ヒトコブラクダ甲状腺の形態学的特徴－鰓後体遺残とC細胞の分布－

  中村鉄平, 市居修, Yaser Hosny Ali Elewa, 細谷実里奈, Wael A. M. Ghonimi, 辰巳治, 長崎健一, 昆泰寛

  第161回日本獣医学会学術集会  2018/09
• 自己免疫疾患モデルマウスの骨に観察される形態機能的変化

  難波貴志, 市居 修, Yaser Hosny Ali Elewa, 中村鉄平, 木村純平, 大谷祐紀, Md. Abdul Masum, 昆 泰寛

  第161回日本獣医学会学術集会  2018/09
• 腎疾患の新知見－Casp3欠損マウスにみられる腎病変－

  鈴木崇史, 市居修, 中村鉄平, Yaser Hosny Ali Elewa, 昆泰寛

  第161回日本獣医学会学術集会  2018/09
• MRL/MpJ-Faslpr/lprマウスの全身自己免疫異常が線毛運動機能に与える影響

  細谷 実里奈, 市居 修, Yaser Hosny Ali Elewa, 中村 鉄平, 昆 泰寛

  第161回日本獣医学会学術集会  2018/09
• 自己免疫疾患モデルマウスで増加する減数分裂特異的精母細胞アポトーシスの原因探索

  大谷祐紀, 市居 修, Yaser Hosny Ali Elewa, 木村純平, Md. Abdul Masum, 中村鉄平, 昆 泰寛

  第161回日本獣医学会学術集会  2018/09
• 新たな腎病態マーカー分子の発見と臨床獣医学への応用に関する研究

  市居 修

  第161回日本獣医学会学術集会  2018/09
• 動物の尿路に出現するリンパ組織（Urinary tract-associated lymphoid tissue, UTALT）

  市居 修, 中村 鉄平, 細谷 実里奈, 堀野 太郎, Yaser Hosny Ali Elewa, 昆 泰寛

  第161回日本獣医学会学術集会  2018/09
• Overexpression of Toll-like receptor 9 correlates with podocyte injury found in murine autoimmune glomerulonephritis

  Md. Abdul Masum, 市居 修, Yaser Hosny Ali Elewa, 中村 鉄平, 大谷 祐紀, 細谷 実里奈, 昆 泰寛

  第161回日本獣医学会学術集会  2018/09
• ウシの眼関連リンパ組織について

  小千田 圭吾, 市居 修, 中村 鉄平, 池田 哲平, 山下 祐輔, 長澤 裕哉, Yaser Hosny Ali Elewa, 昆 泰寛

  第161回日本獣医学会学術集会  2018/09
• Mediastinal fat-associated lymphoid cluster and lung asthma development in papain induced lung asthma mice model

  Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon

  第64回東北・北海道連合支部学術集会  2018/09
• The estimation of potential PCBs toxicity in cats by evaluating CYP450 expressions

  KHIDKHAN Kraisiri, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M, M. Nakayama, Kei Nomiyama, Mitsuyoshi Takiguchi, Nozomu Yokoyama, Osamu Ichii, Shinsuke Tanabe, Mayumi Ishizuka

  Dioxin 2018 : The 38th International Symposium on Halogenated Persistent Organic Pollutants & 10th International PCB Workshop  2018/08
• 雄性コットンラット(Sigmodon hispidus)にみられる糸球体病変

  中村鉄平, 市居 修, 入江隆夫, 孝口裕一, 寸田祐嗣, 堀野太郎, Md. Abdul Masum, 辰巳治, Yaser Hosny Ali Elewa, 昆 泰寛

  第11回 日本獣医腎泌尿器学会学術集会  2018/08
• ネコの尿中exosomeに含まれるマイクロRNAの解析

  市居 修, 大田 寛, 堀野太郎, 中村鉄平, 細谷実里奈, 溝口達也, 森下啓太郎, 中村健介, 佐々木 東, 滝口満喜, 佐藤 遼, 小山田和央, 昆泰寛

  第11回 日本獣医腎泌尿器学会学術集会  2018/08
• 有機ハロゲン化合物曝露によるネコの生 化学マーカーの変化および甲状腺機能に及ぼす影響評価

  田中 啓介, 野見山 桂, 水川 葉月, 高口 倖暉, 田上 瑠美, 横山 望, 市居 修, 滝口 満喜, 中山 翔太, 池中 良徳, 石塚真由美, 国末達也, 田辺 信介

  第27回環境化学討論会  2018/05
• ネコの in vivo BDE209 長期曝露試験による体内動態の解明および甲状腺ホルモンへの影響評価

  田中 啓介, 野見山 桂, 水川 葉月, 高口 倖暉, 田上 瑠美, 横山 望, 市居 修, 滝口 満喜, 中山 翔太, 池中 良徳, 石塚真由美, 国末達也, 田辺 信介

  第27回環境化学討論会  2018/05
• Local CD34-positive capillary decreased with the progression of lesion in respective area of kidney in mice.

  Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon

  The 17th International Conference on Nephrology and Urology  2018/03
• Dual effects of bleomycin on the intra-thoracic immune hemostasis and lung injury in autoimmune disease model mice

  Y. H. A. Elewa, O. Ichii, S, Y. Kon

  The 41st Annual International Conference of Medical Histology & Cell Biology, Regenerative Medicine & Cell Transplantation.  2017/12
• 環境ホルモン学会第20回研究発表会 ポリ塩化ビフェニル（PCBs）がネコの甲状腺機能に及ぼす影響

  水川葉月, 高居名菜, 野見山桂, 高口倖暉, 横山望, 市居修, 滝口満喜, 池中良徳, 中山翔太, 石塚真由美

  環境ホルモン学会第20回研究発表会  2017/12
• Discovery of renal biomarkers in birds by transcriptome analysis and glycomics analysis following kidney injury in chicken model.

  Ishii C, Ikenaka Y, Kawai KY, Ichii O, Nakayama SMM, Mizukawa H, Ishizuka M

  SETAC North America 38th Annual Meeting  2017/11
• ABNORMALITY OF OVULATION AND OOCYTE-PICK-UP IN MRL/MpJ-Faslpr/lpr MICE.

  Marina Hosotani, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Saori Otsuka-Kanazawa, Yasuhiro Kon

  The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA).  2017/10
• BXSB/MpJ-Yaa MICE SHOW THE INCREASE OF APOPTOTIC SPERMATOCYTES IN STAGES Ⅻ SEMINIFEROUS TUBULES.

  Yuki Otani, Osamu Ichii, Yaser Hosny Ali Elewa, Junpei Kimura, Md. Abdul Masum, Teppei Nakamura, Yasuhiro Kon

  The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA).  2017/10
• IL-1F6/IL-36α SIGNALING REGULATES RENAL INFLAMMATION.

  Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon

  The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA).  2017/10
• DUAL EFFECTS OF BLEOMYCIN ON THE INTRA-THORACIC IMMUNE HEMOSTASIS AND LUNG INJURY IN AUTOIMMUNE DISEASE MODEL MICE.

  Yaser Hosny Ali Elewa, Osamu Ichii, Teppei Nakamura, Yasuhiro Kon

  The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA)  2017/10
• 黄色ブドウ球菌死菌の鼻腔粘膜感作による乳腺への液性免疫の誘導とそれによる乳汁中黄色ブドウ球菌の増殖抑制効果

  長澤裕哉, 菊 佳男, 菅原和恵, 遠藤亜矢, 甲斐千暁, 林 智人

  第22回日本乳房炎研究会学術集会  2017/10
• Short-term or long-term in vivo exposure to organohalogen compounds in cats: Elucidate the metabolic capacities and effects on thyroid function

  Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kei Nomiyama, Misaki Maehara, Aksorn Saengtienchai, Tsend-ayush Sainnoxoi, Kraisiri Khidkhan, Nozomu Yokoyama, Kazuyoshi Sasaoka, Osamu Ichii, Mitsuyoshi Takiguchi, Khoki Takaguchi, Hiroki Nishikawa, Nana Takai, Shinsuke Tanabe, Mayumi Ishizuka

  9th International Toxicology Symposium in Nigeria  2017/09
• Discovery of renal biomarker in birds by transcriptome analysis of kidney tissues and glycomics analysis of plasma following renal damage in chicken model.

  Ishii C, Ikenaka Y, Kawai KY, Ichii O, Nakayama, SMM, Mizukawa H, Ishizuka M

  The 5th Sapporo Summer Seminar for One Health  2017/09
• 鳥類医学の発展に向けた新規腎障害マーカーの探索

  石井千尋, 池中良徳, 川合佑典, 市居修, 中山翔太, 西村紳一郎, 大橋哲, 田中誠一, 齊藤慶輔, 渡邊有希子, 水川葉月, 石塚真由美

  日本鳥学会2017年度大会  2017/09
• 黄色ブドウ球菌死菌を抗原とした鼻腔粘膜感作による乳房炎防除効果

  長澤裕哉, 菊佳男, 菅原和恵, 甲斐千暁, 澤田晋一, 秋吉一成, 林智人

  第160回日本獣医学会学術集会  2017/09
• Sarcocystis属原虫の終宿主候補としてのキタキツネにおける調査

  入江隆夫, 浦口宏二, 中村鉄平, 市居 修, 髙井伸二, 八木欣平

  2017/09
• Pathological correlations between endothelial cells and podocytes in autoimmune-related injury of the mouse glomerulus

  Md. Abdul Masum, 市居 修, Yaser Hosny Ali Elewa, 中村 鉄平, 昆 泰寛

  第160回日本獣医学会  2017/09
• BXSB/MpJ-Yaaマウスにみられる精母細胞のアポトーシス－自己免疫異常との関連性－  [Not invited]

  大谷 祐紀, 市居 修, Yaser Hosny Ali Elewa, 木村 純平, Md. Abdul Masum, 中村 鉄平, 昆 泰寛

  第160回日本獣医学会  2017/09
• MRL/MpJマウスの排卵―黄体形成過程にみられる特異な表現型

  細谷 実里奈, 市居 修, Yaser Hosny Ali Elewa, 中村 鉄平, 昆 泰寛

  第160回日本獣医学会  2017/09
• Dual effects of bleomycin on the intra-thoracic immune hemostasis and lung injury in autoimmune disease model mice.

  Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon

  The 63th annual meeting of the Japanese the Anatomical Society.  2017/09
• Histopathological features observed in the testis of autoimmune-prone BXSB/MpJ-Yaa mice.

  Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon

  The 5th Sapporo Summer Seminar for One Health (SaSSOH)  2017/09
• Loss of endothelial fenestration correlates with podocyte injury in the mouse model of membranoproliferative glomerulonephritis.

  Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon. T

  The 5th Sapporo Summer Seminar for One Health (SaSSOH)  2017/09
• Mechanism and abnormality of ovulation and picking up of mammalian oocytes-Immune factors affecting the molecular morphology of the oviduct

  M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon

  The 5th Sapporo Summer Seminar for One Health (SaSSOH)  2017/09
• Effects of Organohalogen Compounds on Serum Biochemical Profiles in Cats Kraisiri Khidkhan

  Hazuki Mizukawa, Kei Nomiyama, Yoshinori Ikenaka, Shota M.M. Nakayama, Nozomu Yokoyama, Kazuyoshi Sasaoka, Osamu Ichii, Mitsuyoshi Takiguchi, Hiroyuki Nishikawa, Keisuke Tanaka, Kohki Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  The 5th Sapporo Summer Seminar for One Health (SaSSOH)  2017/09
• In vivo exposure to PCBs in cats: Analysis of metabolic capacities and effects on the thyroid hormone homeostasis

  Hazuki Mizukawa, Kei Nomiyama, Hiroyuki Nishikawa, Misaki Maehara, Nana Takai, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kohki Takaguchi, Shinsuke Tanabe, Mayumi Ishizuka

  37th International Symposium on Halogenated Persistent Organic Pollutants (DIOXIN 2017)  2017/08
• 雌性コットンラット(Sigmodon hispidus)にみられる慢性腎臓病－子宮蓄膿症及び性ホルモンの関与－

  中村鉄平, 市居 修, 入江隆夫, 孝口裕一, 寸田祐嗣, 堀野太郎, 辰巳治, Yaser Hosny Ali Elewa, 昆 泰寛

  第10回日本獣医腎泌尿器学会  2017/08
• 尿細管間質病変に関与するIL-36シグナリング

  市居 修, 木村 純平, 岡村 匡史, 堀野 太郎, 中村 鉄平, 矢吹 映, 佐々木 隼人, Yaser Hosny Ali Elewa, 昆 泰寛

  第10回日本獣医腎泌尿器学会  2017/08
• ネコの甲状腺機能に対するポリ塩化ビフェニル（PCBs）の影響評価〜甲状腺ホルモンの脱ヨード化と代謝能の解析  [Not invited]

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 中山翔太, Tsend-ayush Sainnoxoi, 田辺信介, 石塚真由美

  第44回日本毒性学会  2017/07
• イエネコのin vivo長期曝露試験：デカブロモジフェニルエーテ (BDE209)の生体内変化  [Not invited]

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, Aksorn Saengtienchai,Tsend-ayush Sainnoxoi, 横山望, 市居 修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介

  第26回環境化学討論会  2017/06
• PCBs曝露 がイヌ・ネコの甲状腺ホルモン恒常性へ及ぼす影響  [Not invited]

  高口 倖暉, 野見山 桂, 西川 博之, 水川 葉月, 田上 瑠美, 芳之内 結加, 横山 望, 市居 修, 滝口満喜, 中山 翔太, 池中良徳, 石塚真由美, 岩田久人, 国末達也, 田辺信介

  第26回環境化学討論会  2017/06
• 血清中メタボローム解析によるイエネコのPCBs毒性影響評価  [Not invited]

  野見山桂, 西川 博之, 水川葉月, 高口倖暉, Tsend-ayush Sainnoxoi, 横山 望, 市居 修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介

  第26回環境化学討論会  2017/06
• ポリ塩化ビフェニル（PCBs）暴露によるネコ甲状腺機能への影響評価 〜 甲状腺ホルモンの脱ヨード化と代謝能解析〜  [Not invited]

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 中山翔太, Tsend-ayush Sainnoxoi, 田辺信介, 石塚真由美

  第26回環境化学討論会  2017/06
• ウシ生体内で形成させた移植医療用組織の構造  [Not invited]

  今山知佳, 鈴木貴弘, 小林 謙, 三谷朋弘, 市居 修, 小千田圭吾, 池田哲平, 寺澤 武, 中山泰秀

  日本畜産学会第122回大会  2017/03
• 家畜生体内を利用して再生移植医療用組織をつくる  [Not invited]

  西邑隆徳, 今山知佳, 鈴木貴弘, 小林 謙, 三谷朋弘, 市居 修, 小千田圭吾, 池田哲平, 寺澤 武, 中山泰秀

  日本畜産学会第122回大会  2017/03
• RNAから展開する腎臓病研究 〜 獣医臨床へのアプローチ〜  [Invited]

  市居 修

  第13回日本獣医内科学アカデミー 学術大会  2017/02
• 腎臓病を知らせる microRNA −病態マーカーとしての可能性と問題点−  [Invited]

  市居 修

  第33回日本毒性病理学会学術集会  2017/01
• 生体内組織形成術による管状組織体の壁厚制御  [Not invited]

  寺澤 武, 西邑 隆徳, 三谷 朋弘, 市居 修, 中山 泰秀

  第54回日本人工臓器学会大会  2016/11
• Characteristic for biotransformation of polychrolinated biphenyls in cats  [Not invited]

  Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Hiroyuki Nishikawa, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kohki Takaguchi, Shinsuke Tanabe, Mayumi Ishizuka

  The 7th SETAC World Congress/37th SETAC North America Annual Meeting  2016/11
• ウシの咽頭扁桃は鼻腔から投与した黄色ブドウ球菌死菌に対する免疫応答の場となる  [Not invited]

  長澤 裕哉, 菊 佳男, 田邉 扶由子, 菅原 和恵, 石川 義春, 市居 修, 昆 泰寛, 門田 耕一, 林 智人

  第21回日本乳房炎研究会・学術集会  2016/10
• In vivo analysis of PCB metabolic capacities and effects on the thyroid hormone in cats  [Not invited]

  Hazuki, Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Hiroyuki Nishikawa, Kohki Takaguchi, Aksorn Saengtienchai, Tsend-ayush Sainnoxoi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Shinsuke Tanabe, Mayumi Ishizuka

  The 9th International PCB Workshop  2016/10
• コットンラットの咽頭喉頭部,甲状腺及びその周囲組織にみられる形態学的特徴  [Not invited]

  中村 鉄平, 入江 隆夫, 市居 修, 篠原 明男, 孝口 裕一, 越本 知大, 長崎 健一, 昆 泰寛

  日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
• マウス十二指腸空腸曲の形態形成機序の解析  [Not invited]

  尾之内佐和, 市居 修, 昆 泰寛

  日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
• 自己免疫疾患が卵管の卵子捕捉機能に及ぼす影響について  [Not invited]

  細谷 実里奈, 市居 修, 中村 鉄平, Yaser Hosny Ali Elewa, 昆 泰寛

  日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
• 遠位尿細管上皮細胞の形態機能を制御するIL-1F6/IL-36α  [Not invited]

  居 修, 中村鉄平, 岡村匡史, 木村純平, 堀野太郎, 昆 泰寛

  日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
• Effect of H2S on 5-HT release from glomus cells in the chicken thoracic aorta  [Not invited]

  Dugar DELGERMURUN, 山口 聡一郎, 市居 修, 昆 泰寛, 伊藤 茂男, 乙黒 兼一

  第159回 日本獣医学会学術集会  2016/09
• 抗ワクモ（Dermanyssus gallinae）ワクチン開発に向けたワクモ由来フェリチン2の性状解析  [Not invited]

  伊勢崎 政美, 村田 史郎, 酒井 英史, 矢吹 卓也, 種子野 章, 市居 修, 伊東 拓也, 今内 覚, 大橋 和彦

  第159回 日本獣医学会学術集会  2016/09
• 芳香族炭化水素受容体シグナルの活性化は胃粘膜異常を増悪する  [Not invited]

  團塚 愛, Annika Hanberg, 市居 修, 中村 鉄平, 昆 泰寛

  第159回 日本獣医学会学術集会  2016/09
• マウス遠位尿細管の嚢胞形成に関与する新規原因遺伝子座の役割  [Not invited]

  市居 修, 中村 鉄平, 矢吹 映, 堀野 太郎, 昆 泰寛

  第159回 日本獣医学会学術集会  2016/09
• ウシ咽頭扁桃は鼻腔投与した黄色ブドウ球菌に対する免疫応答の場になる  [Not invited]

  長澤 裕哉, 菊 佳男, 田邉 扶由子, 菅原 和恵, 石川 義春, 野地 智法, 市居 修, 昆 泰寛, 麻生 久, 門田 耕一, 林 智人

  第159回 日本獣医学会学術集会  2016/09
• Histopathological correlations between the mediastinal fat associated lymphoid clusters and bleomycin-induced pneumonitis in mice  [Not invited]

  Y. H. A. Elewa, Md. A. Masum, T. Nakamura, O. Ichii, Y. Kon

  第159回 日本獣医学会学術集会  2016/09
• CD34-positive capillary decreased with the progression of kidney disease in mouse models  [Not invited]

  Masum Md. Abdul, Elewa YH, 市居 修, 昆 泰寛

  第159回 日本獣医学会学術集会  2016/09
• 自己免疫疾患モデルMRL/MpJ-Faslprマウスにみられる卵子のキャッチアップ障害  [Not invited]

  細谷 実里奈, 市居 修, 中村 鉄平, Yaser Hosny Ali Elewa, 昆 泰寛

  第159回 日本獣医学会学術集会  2016/09
• マウス胎 子腸管器官培養法により形成された十二指腸空腸曲の解析  [Not invited]

  尾之内佐和, 市居 修, 昆 泰寛

  第159回 日本獣医学会学術集会  2016/09
• コットンラットにおけるインスリン抵抗性と脂肪蓄積との関連  [Not invited]

  中村 鉄平, 市居 修, 入江 隆夫, 寸田 祐嗣, 孝口 裕一, 長崎 健一, 吉安 友二, 昆 泰寛

  第159回 日本獣医学会学術集会  2016/09
• 犬と猫の慢性腎臓病における尿細管周囲毛細血管の変化  [Not invited]

  中村麗菜, 矢吹 映, 市居 修, 水川葉月, 横山 望, 大和 修

  第159回 日本獣医学会学術集会  2016/09
• Activation of Ahr signaling pathway aggravates the mucosal abnormality in stomach  [Not invited]

  Ai Dantsuka, Annika Hanberg, Osamu Ichii, Yasuhiro Kon

  The 4th Sapporo Summer Seminar for One Health  2016/09
• CD34-positive capillary decreased with the progression of kidney disease in mice  [Not invited]

  Masum Md. Abdul, Elewa YH, Ichii O, Kon Y

  The 4th Sapporo Summer Seminar for One Health  2016/09
• Analysis of the mouse duodenojejunal flexure using the fetal gut organ culture system  [Not invited]

  Onouchi S, Ichii O, Kon Y

  The 4th Sapporo Summer Seminar for One Health  2016/09
• The effect of environmental pollutants to pet animals ~Level and effects of Persistent organic pollutants (POPs) to domestic ca  [Not invited]

  Tsend-ayush Sainnokhoi, Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Aksorn Saengtienchai, Shinsuke Tanabe, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka

  The 4th Sapporo Summer Seminar for One Health  2016/09
• イヌの尿中exosomeに含まれるマイクロRNA - 病態マーカーとしての可能性 ?  [Not invited]

  市居修, 大田寛, 堀野太郎, 中村鉄平, 細谷実里奈, 溝口達也, 森下啓太郎, 中村健介, 星野有希, 高木哲, 佐々木東, 滝口満喜, 佐藤遼, 小山田和央, 昆泰寛

  第9回 日本獣医腎泌尿器学会学術集会  2016/08
• 雌性コットンラット(Sigmodon hispidus)にみられる腎性貧血  [Not invited]

  中村 鉄平, 市居 修, 入江 隆夫, 孝口 裕一, 寸田 祐嗣, 堀野 太郎, 昆 泰寛

  第9回 日本獣医腎泌尿器学会学術集会  2016/08
• Metabolic capacities of polychlorinated biphenyls (PCBs) in cats and dog  [Not invited]

  Hazuki Mizukawa, Kei Nomiyama, Shinsuke Tanabe, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka, M

  The 8th international Toxicology symposium in Africa  2016/08
• ポリ塩化ビフェニル（PCBs）のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価  [Not invited]

  水川 葉月, 前原 美咲, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 西川 博之, 池中 良徳, 中山 翔太, 高口 倖暉, 田辺 信介, 石塚 真由美

  第43回日本毒性学会学術年会  2016/06
• メタボローム解析を用いたPCBsによるイエネコの毒性影響評価  [Not invited]

  西川博之, 野見山桂, 水川葉月, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介

  第25回環境化学討論会  2016/06
• ネコにおけるポリ塩化ビフェニル（PCBs）の異物代謝機構解明と甲状腺ホルモンへの影響評価  [Not invited]

  水川葉月, 前原美咲, 横山望, 市居修, 滝口満喜, 野見山桂, 西川博之, 池中良徳, 中山翔太, 高口倖暉, 田辺信介, 石塚真由美

  第25回環境化学討論会  2016/06
• Mouse duodenojejunal flexure formation with asymmetric morphologies between the inner and outer bending sides  [Not invited]

  Onouchi S, Ichii O, Kon Y

  JSDB Special Symposium: Frontier of Developmental Biology Hosted by JSDB  2016/06
• SEM法を利用した腎生検の迅速電子顕微鏡診断への応用  [Not invited]

  髙木 孝士, 城 謙輔, 大野 伸彦, 齊藤 成, Thai Quynh T, 昆 泰寛, 市居 修, Yeser Hosny Ali Elewa H, 笹野 公伸

  第105回日本病理学会総会  2016/05
• Immune system via novel mediastinal fat associated lymphoid clusters in mice  [Not invited]

  Y. H. A. Elewa, O. Ichii, Y. Kon

  The Scientific Symposium  2016/03
• Sex-related difference of the mediastinal fat associated lymphoid clusters in MRL/MpJ-Faslpr autoimmune disease model mice.  [Not invited]

  Y. H. A. Elewa, O. Ichii, Y. Kon

  The 11th Scientific Vet. Med. (second international) conference  2016/03
• TO ACCELERATE A GLOBAL NETWORK OF ENVIRONMENTAL RESEARCHERS BIOTRANSFORMATION POTENCIES OF POLYCHLORINATED BIPHENYLS IN CATS  [Not invited]

  Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Yoshinori Ikenaka, Shouta M.M.Nakayama, Shinsuke Tanabe, Mayumi Ishizuka

  INTERNATIONAL SYMPOSIUM ON ENVIRONMENTAL CHEMISTRY AND TOXICOLOGY  2016/03
• Metabolism and biotransformation of organohalogen compounds in the liver microsomes of cats and dogs  [Not invited]

  Hazuki Mizukawa, Kei Nomiyama, Nozomu, Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M, Nakayama, Misaki Maehara, Shinsuke Tanabe, Mayumi Ishizuka

  SETAC North America 36th Annual Meeting  2015/11
• ミニチュア・ダックスフンドの炎症性結直腸ポリープ症例の結直腸粘膜におけるToll-like receptor 2,4の局在解析  [Not invited]

  横山 望, 大田 寛, 賀川 由美子, 山崎 淳平, 市居 修, Nisa Khoirun, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 中村 健介, 滝口 満喜

  第158回 日本獣医学会学術集会  2015/09
• マウス十二指腸空腸曲の細胞外基質は屈曲形成と共に変遷する  [Not invited]

  尾之内佐和, 市居 修, 昆 泰寛

  第158回 日本獣医学会学術集会  2015/09
• 日本獣医学会学術集会 遠位尿細管傷害を知らせるマーカー分子“IL-1F6/IL-36a”の有用性  [Not invited]

  市居 修, 中村 鉄平, 堀野 太郎, 木村 純平, 岡村 匡史, 昆 泰寛

  第158回 日本獣医学会学術集会  2015/09
• Gut morphogenesis in mice ?spatiotemporal distribution of the extracellular matrix changes during duodenojejunal flexure formation  [Not invited]

  Onouchi S, Ichii O, Kon Y

  The 3rd Sapporo Summer Seminar for One Health  2015/09
• 尿中exosome由来microRNAの解析−動物種横断的腎障害マーカーになるか？−  [Not invited]

  市居修, 大田寛, 堀野太郎, 中村鉄平, 細谷実里奈, 溝口達也, 森下啓太郎, 中村健介, 佐々木東, 滝口満喜, 佐藤遼, 小山田和央, 昆泰寛

  第8回 日本獣医腎泌尿器学会学術集会  2015/08
• Interleukin 1 family, member 6 is a useful histopathological diagnostic marker in acute kidney injury  [Not invited]

  O. Ichii, D. Shiozuru, S. Otsuka-Kanazawa, Y. Kon

  The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
• Biased distribution of ovarian mast cells alter the early follicular development in postnatal MRL/MpJ mice  [Not invited]

  T. Nakamura, O. Ichii, S. Otsuka-Kanazawa, K. Nagasaki, Y. Kon

  The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
• A novel mouse mediastinal fat-associated lymphoid tissue and its relationship with autoimmune disease  [Not invited]

  Y. H.A. Elewa, S. Otsuka-Kanazawa, O. Ichii, Y. Kon

  The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
• Autosomal causative locus for production of testicular oocytes in MRL/MpJ mice  [Not invited]

  Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon

  The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
• Validation of the function of MRL/MpJ mouse-derived loci in the spermatogenesis under testicular hyperthermia  [Not invited]

  M. Chihara, S. Otsuka, O. Ichii, Y. Kon

  The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
• Spatiotemporal distribution of the extracellular matrix in the fetal mouse duodenojejunal flexure  [Not invited]

  S. Onouchi, O. Ichii, S. Otsuka-Kanazawa, Y. Kon

  The 2nd Sapporo Summer Seminar for One Health  2015/02
• Greb1, a Gene Responsible for the Development of Renal Cysts Originating in the Distal Tubules in DBA/2 Mice  [Not invited]

  Osamu Ichii, Saori Otsuka, Akira Yabuki, Taro Horino, Teppei Nakamura, Yasuhiro Kon

  American Society of Nephrology  2014/11
• Toll-Like Receptor 8 Contributes to Podocyte Injury in Murine Autoimmune Glomerulonephritis  [Not invited]

  Junpei Kimura, Osamu Ichii, Teppei Nakamura, Taro Horino, Saori Otsuka, Yasuhiro Kon

  American Society of Nephrology  2014/11
• 足細胞の機能形態を制御するmiR-26a −糸球体傷害のバイオマーカー核酸になり得る−  [Not invited]

  市居 修, 大塚沙織, 中村鉄平, 木村 純平, 堀野 太郎, 昆 泰寛

  第7回日本獣医腎泌尿器学会学術集会  2014/09
• miR-26a − 腎糸球体上皮細胞の機能形態を制御する短鎖RNA  [Invited]

  市居 修

  第157回 日本獣医学会学術集会 日本獣医解剖学会シンポジウム  2014/09
• Characterization of mouse mediastinal fat-associated lymphoid clusters (english)  [Not invited]

  Yaser Hosny Ali Elewa, 市居 修, 大塚 沙織, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• Greb1 −DBA/2Crマウスに出現する遠位尿細管由来嚢胞の原因遺伝子候補−  [Not invited]

  市居 修, 大塚 沙織, 矢吹 映, 堀野 太郎, 中村 鉄平, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• 自己免疫疾患モデルMRL/MpJ-lprマウスの卵巣は機能形態異常を示す  [Not invited]

  大谷 祐紀, 市居 修, 大塚 沙織, 中村 鉄平, 千原 正尚, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• マウス十二指腸空腸曲における屈曲内−外側の形態学的差異  [Not invited]

  尾之内 佐和, 市居 修, 大塚 沙織, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• 腎障害時にみられるMRL/MpJマウスの特別な修復過程について  [Not invited]

  塩水流 大地, 市居 修, 中村 鉄平, 大塚 沙織, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• Toll-like receptor 8は自己免疫性糸球体腎炎の足細胞傷害に関与する  [Not invited]

  木村 純平, 市居 修, 大田 寛, 中村 鉄平, 堀野 太郎, 大塚 沙織, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• 新生子MRL/MpJマウスにおける卵巣内肥満細胞の由来?卵巣-卵巣采結合部から出現する可能性?  [Not invited]

  中村 鉄平, 千原 正尚, 市居 修, 大塚 沙織, 長崎 健一, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• MRL/MpJマウスに出現する精巣内卵細胞のエピゲノム解析  [Not invited]

  大塚 沙織, 市居 修, 昆 泰寛

  第157回 日本獣医学会学術集会  2014/09
• Toll-like receptor 8 contributes to podocyte injury in murine autoimmune glomerulonephritis  [Not invited]

  Junpei Kimura, Osamu Ichii, Saori Otsuka, Yasuhiro Kon

  The 2nd Sapporo Summer Seminar for One Health  2014/09
• 腎障害モデルにおける腎組織修復過程の観察 −MRL/MpJマウスが具備する創傷治癒形質との関連−  [Not invited]

  塩水流大地, 市居 修, 中村鉄平, 大塚沙織, 昆 泰寛

  第7回日本獣医腎泌尿器学会学術集会  2014/08
• 伴侶動物の腎臓におけるToll-like receptor8の発現解析 -糸球体足細胞傷害に関与するバイオセンサー-  [Not invited]

  木村 純平, 市居 修, 大田 寛, 横山 望, 森下 啓太郎, 星野 有希, 高木 哲, 大塚 沙織, 昆 泰寛

  第7回日本獣医腎泌尿器学会学術集会  2014/08
• The candidate factors for the development of chronic kidney disease.  [Not invited]

  Osamu Ichii, Saori Otsuka, Yasuhiro Kon

  The 16th SNU-HU Symposium Current Advances in Veterinary Medicine.  2013/12
• MRL/MpJマウスに出現する肥満細胞  [Not invited]

  中村鉄平, 市居 修, 大塚沙織, 昆 泰寛

  日本解剖学会第59回東北・北海道連合支部学術集会  2013/09
• マウスにおける十二指腸空腸曲形成機序の解析  [Not invited]

  尾之内佐和, 市居 修, 大塚沙織, 昆 泰寛

  日本解剖学会第59回東北・北海道連合支部学術集会  2013/09
• 伴侶動物の腎臓に発現するmiRNAのデータベース構築−動物種共通のバイオマーカー開発を目指して  [Not invited]

  市居 修, 大塚沙織, 矢吹 映, 大田 寛, 堀野太郎, 昆 泰寛

  第156回 日本獣医学会学術集会  2013/09
• 慢性膵炎の系統差に関する研究-MRLマウス1番染色体テロメア領域の影響  [Not invited]

  岡田祐樹, 市居 修, 大塚 沙織, 昆 泰寛

  第156回 日本獣医学会学術集会  2013/09
• MRL/MpJマウスの卵細胞発育を制御する遺伝学的因子  [Not invited]

  山下由真, 市居 修, 大塚沙織, 昆 泰寛

  第156回 日本獣医学会学術集会  2013/09
• ビタミンA欠乏食給餌マウスからみる精細胞−血液精巣関門の相互作用  [Not invited]

  千原正尚, 市居 修, 大塚沙織, 昆 泰寛

  第156回 日本獣医学会学術集会  2013/09
• マウス消化管の発生に関する研究 〜どうして腸管は曲がるのか?〜  [Not invited]

  尾之内 佐和, 市居 修, 大塚 沙織, 橋本 善春, 昆 泰寛

  第154回 日本獣医学会学術集会  2013/09
• The uremic toxin indoxyl sulfate causes podocyte injury in vivo and in vitro  [Not invited]

  Osamu Ichii, Huiyan Lu, Hideko Takahashi, Patricia Zerfas, Jeffrey Kopp

  Kidney week 2013, American Society of Nephrology  2013/09
• 腎臓病のmicroRNA解析―動物種共通のバイオマーカー開発を目指して―  [Not invited]

  市居 修, 大塚沙織, 中村鉄平, 堀野太郎, 昆 泰寛

  第6回日本獣医腎泌尿器学会学術集会  2013/08
• 糸球体腎炎モデルマウスの足細胞傷害 - Toll-like receptor ファミリーの関与  [Not invited]

  木村純平, 市居 修, 大塚沙織, 昆 泰寛

  第6回日本獣医腎泌尿器学会学術集会  2013/08
• 糸球体病変を制御するmiRNAの探索−動物種共通のバイオマーカー開発を目指して−  [Not invited]

  市居 修, 大塚沙織, 中村鉄平, 野元由佳, 橋本善春, 堀野太郎, 昆 泰寛

  第155回 日本獣医学会学術集会  2013/03
• 糸球体腎炎モデルマウスにおける足細胞傷害の解析  [Not invited]

  木村純平, 市居 修, 大塚沙織, 佐々木隼人, 橋本善春, 昆 泰寛

  第155回 日本獣医学会学術集会  2013/03
• 熱ショック誘導性の精細管腔内石灰沈着の発生機序と抑制因子の解析  [Not invited]

  千原正尚, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛

  第155回 日本獣医学会学術集会  2013/03
• MRLマウス肥満細胞は新生子期の卵形成に関与する  [Not invited]

  中村鉄平, 市居 修, 大塚沙織, 坂田侑子, 長崎健一, 橋本善春, 昆 泰寛

  第155回 日本獣医学会学術集会  2013/03
• Initiation of meiosis in fetal testis of MRL mouse to produce testicular oocyte  [Not invited]

  Saori Otsuka, Osamu Ichii, Nobuya Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon

  第4回アジア獣医解剖学会  2012/10
• Mast cells in neonatal ovary -a new unique phenotype of MRL/MpJ mice-  [Not invited]

  Teppei NAKAMURA, Yuko SAKATA, S. Saori OTSUKA, Osamu ICHII, Kenichi NAGASAKI, Yoshiharu HASHIMOTO, Yasuhiro KON

  第4回アジア獣医解剖学会  2012/09
• Analysis of claudin-3 expression and function during the murine spermatogenesis.  [Not invited]

  Masataka CHIHARA, Saori OTSUKA, Osamu ICHII, Yoshiharu HASHIMOTO, Yasuhiro KON

  第4回アジア獣医解剖学会  2012/09
• 尿毒症物質インドキシル硫酸は腎糸球体上皮細胞傷害に関与する―芳香族炭化水素受容体のリガンド作用―  [Not invited]

  市居 修, 若新 英史, 村上 太一, 堀野 太郎, Huiyan Lu, Hideko Takahashi, Zerfas Patricia, 大塚 沙織, 橋本 善春, 昆 泰寛, Jeffrey Kopp

  第154回 日本獣医学会学術集会  2012/09
• 高温曝露後の精巣における減数分裂の進行と精細管腔内に出現する石灰沈着  [Not invited]

  千原 正尚, 市居 修, 大塚 沙織, 橋本 善春, 昆 泰寛

  第154回 日本獣医学会学術集会  2012/09
• マレック病感染鶏由腫瘍病変部における免疫抑制因子PD-1/PD-L1発現の形態学的解析  [Not invited]

  村田史郎, 松山あゆみ, 伊勢崎 政美, 高崎紗蘭, 市居 修, 今内 覚, 大橋和彦

  第154回 日本獣医学会学術集会  2012/09
• MRLマウス胎子精巣における卵細胞形成過程の解析  [Not invited]

  大塚沙織, 市居 修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛

  第58回東北・北海道連合支部学術集会  2012/08
• Indoxyl sulfate: a uremic toxin and aryl-hydrocarbon receptor ligand that may cause podocyte injury  [Not invited]

  Osamu Ichii, Jeffrey B Kopp

  National Kidney Foundation, 21st Annual Fellows Research Forum  2012/06
• Indoxyl sulfate: a uremic toxin and aryl-hydrocarbon receptor ligand that may cause podocyte injury  [Not invited]

  Osamu Ichii, Jeffrey Kopp

  The 7th annual NIDDK Fellows Retreat, NIH  2012/04
• MRL/MpJマウスの卵巣内肥満細胞出現に関与する遺伝的因子の解析  [Not invited]

  中村鉄平, 坂田侑子, 大塚沙織, 市居 修, 並木由佳, 長崎健一, 橋本善春, 昆 泰寛

  第153回 日本獣医学会学術集会  2012/03
• マウス精巣における密着結合蛋白claudin-3の局在および機能解析  [Not invited]

  千原正尚, 市居 修, 大塚沙織, 並木由佳, 池渕良洋, 橋本善春, 昆 泰寛

  第153回 日本獣医学会学術集  2012/03
• High-Resolution Linkage Mapping of the Rat Hooded Locus  [Not invited]

  Torigoe Daisuke, Ichii Osamu, Ruihua Dang, Ohnaka Takayuki, Okano Shinya, Kon Yasuhiro, Sasaki Nobuya, Agui Takashi

  61st The American Association for Laboratory Animal Science  2011/10
• 節足動物DNAのリボゾームRNA遺伝子ITS領域のサイズ分析による生物種同定の試み  [Not invited]

  佐藤福太郎, 遠藤大二, 吉村貴行, 伊東拓也, 長 雄一, 浅川満彦, 昆 泰寛, 市居 修, 大塚沙織, 林 正信

  第152回 日本獣医学会学術集会  2011/09
• マウス涙腺炎における涙液を使った病態解析  [Not invited]

  小千田圭吾, 市居 修, 大塚沙織, 並木由佳, 橋本善春, 昆 泰寛

  第152回 日本獣医学会学術集会  2011/09
• マウス心筋発生過程に出現するTUNEL陽性細胞の解析  [Not invited]

  長沼佑季, 市居 修, 大塚沙織, 並木由佳, 橋本善春, 昆 泰寛

  第152回 日本獣医学会学術集会  2011/09
• MRLマウス新生子卵巣に出現する肥満細胞の系統差解  [Not invited]

  中村鉄平, 市居 修, 大塚沙織, 並木由佳, 坂田侑子, 長崎健一, 服部秀樹, 橋本善春, 昆 泰寛

  第152回 日本獣医学会学術集会  2011/09
• 糸球体腎炎モデルマウスにおける尿中脱落細胞の動態解析  [Not invited]

  木村純平, 市居 修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆 泰寛

  第57回 日本解剖学会 東北・北海道連合支部学術集会  2011/08
• ラット頭巾斑責任遺伝子の同定  [Not invited]

  鳥越 大輔, 市居 修, 党 瑞華, 佐々木 宣哉, 昆 泰寛, 安居院 高志

  北海道実験動物研究会・日本実験動物技術者協会北海道支部 合同学術集会 2011  2011/07
• 節足動物DNAのITS領域サイズ分析による生物種同定の試み  [Not invited]

  遠藤大二, 吉村貴行, 佐藤福太郎, 伊東拓也, 長 雄一, 浅川満彦, 昆 泰寛, 市居 修, 大塚沙織, 林 正信

  第151回 日本獣医学会学術集会  2011/03
• 腎症候性出血熱の致死的感染モデルの開発とその病態解析  [Not invited]

  瀬戸隆弘, 吉川佳佑, 真田崇弘, Ngonda Saasa, 尾崎由佳, 市居 修, 好井健太朗, 昆 泰寛, 苅和宏明

  第151回 日本獣医学会学術集会  2011/03
• MRL/MpJマウスにおける卵巣網由来卵巣?腫の経時的観察  [Not invited]

  李 愼曉, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛

  第151回 日本獣医学会学術集会  2011/03
• MRLマウス新生子卵巣における肥満細胞の出現  [Not invited]

  中村鉄平, 市居 修, 大塚沙織, 並木由佳, 長崎健一, 服部秀樹, 橋本善春, 昆 泰寛

  第151回 日本獣医学会学術集会  2011/03
• 129+Ter/Svマウスの遺伝的背景は腎糸球体硬化症に抵抗性である  [Not invited]

  西野智博, 佐々木宣哉, 長崎健一, 市居 修, 昆 泰寛, 安居院高志

  第151回 日本獣医学会学術集  2011/03
• 慢性腎臓病におけるmicroRNAの発現解析−腎間質病変に関与するmiR-146a−  [Not invited]

  市居 修, 大塚沙織, 並木由佳, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛

  第151回 日本獣医学会学術集会  2011
• マウス血液精巣関門関連分子の局在と動態 ―claudin-3, -11, occludin, ZO-1の発現解析  [Not invited]

  千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛

  第56回日本解剖学会 東北・北海道連合支部学術集会  2010/09
• MRLマウスの精巣内卵細胞出現に関与する遺伝的因子の解析  [Not invited]

  大塚沙織, 市居 修, 佐々木宣哉, 並木 由佳, 橋本善春, 遠藤大二, 昆 泰寛

  第150回 日本獣医学会学術集会  2010/09
• 尿中脱落細胞の動態は腎疾患の増悪と相関する‐糸球体腎炎モデルの解析  [Not invited]

  木村純平, 市居 修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆 泰寛

  第150回 日本獣医学会学術集会  2010/09
• Comparative analysis of the expression of aquaporin family between pre- and post-weaning periods in goat major salivary glands  [Not invited]

  Elewa Yaser, 市居 修, 大塚沙織, 金澤智則, 李 愼曉, 並木由佳, 昆 泰寛, 橋本善春

  第150回 日本獣医学会学術集会  2010/09
• 慢性腎臓病における糸球体上皮細胞傷害の解析―腎機能とスリット膜関連分子の動態はイヌとネコで異なる―  [Not invited]

  市居 修, 矢吹 映, 佐々木宣哉, 大塚沙織, 大田 寛, 山崎真大, 滝口満喜, 並木由佳, 橋本善春, 遠藤大二, 昆 泰寛

  第3回 日本獣医泌尿器学会学術集会  2010/07
• MRLマウス胎子精巣内における減数分裂開始と精巣内卵細胞の出現  [Not invited]

  大塚沙織, 市居 修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛

  第149回 日本獣医学会学術集会  2010/03
• Age related structural changes of parotid salivaly glands in goat  [Not invited]

  Yaser Elewa, 橋本善春, 市居 修, 大塚沙織, 金澤智則, 昆 泰寛

  第149回 日本獣医学会学術集会  2010/03
• マウスのネフロン形成過程における間葉‐上皮転換（MET）の解  [Not invited]

  金澤智則, 大塚沙織, 市居 修, 橋本善春, 昆 泰寛

  第149回 日本獣医学会学術集  2010/03
• Pathological differences between dog and cat in renal disease -slit membrane molecules and renal dysfucntion-  [Not invited]

  149th Meeting of the Japanease Society of Veterinary Science  2010
• DBA/2マウスの腎臓における遠位尿細管上皮傷害 -多発性嚢胞腎の早期病変としての可能性-  [Not invited]

  市居 修, 大塚沙織, 矢吹 映, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆 泰寛

  第150回 日本獣医学会学術集会  2010
• イヌおよびネコの腎疾患における病態差 −腎機能とスリット膜関連分子の動態−  [Not invited]

  市居 修, 佐々木宣哉, 矢吹 映, 大田 寛, 滝口満喜, 大塚沙織, 橋本善春, 遠藤大二, 昆 泰寛

  第149回日本獣医学会学術集会  2010
• マウス精子形成過程における血液精巣関門構成分子の動態  [Not invited]

  千原正尚, 市居修, 大塚沙織, 橋本善春, 昆 泰寛

  平成21年度 日本顕微鏡学会 北海道支部学術講演会  2009/12
• MRL/MpJマウスに出現する精巣内卵細胞の解析  [Not invited]

  大塚沙織, 市居 修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛

  平成21年度 日本顕微鏡学会  2009/12
• Age-related structural changes of parotid salivary glands in goat.  [Not invited]

  Elewa Y, Ichii O, Otsuka S, Kanazawa T, Kon Y, Hashimoto Y

  平成21年度 日本顕微鏡学会  2009/12
• Quantitative trait loci analysis of development of ovarian cyst originated from rete ovarii  [Not invited]

  李 愼曉, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛

  第3回 アジア獣医解剖学会  2009/11
• マウス精子形成過程における血液精巣関門構成分子の動態  [Not invited]

  千原正尚, 大塚沙織, 市居 修, 橋本善春, 昆 泰寛

  第148回 日本獣医学会学術集会  2009/11
• Development of innovative method for diagnosis renal disease - Analysis of urinary cells in model mice -  [Not invited]

  木村純平, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛

  Hokkaido University International Symposium on Sustainability Weeks 2009  2009/11
• MRL/MpJマウスに見られる卵巣網由来卵巣嚢腫の量的形質遺伝子座解析  [Not invited]

  李 愼曉, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛

  第147回 日本獣医学会学術集会  2009/04
• Hydronephrosis in (C57BL/6 x DBA/2) mice  [Not invited]

  148th Meeting of the Japanease Society of Veterinary Science  2009
• New diagnosis method for renal disease -Interleukin 1 family member 6 is a biomarker for tubular injury-  [Not invited]

  147th Meeting of the Japanease Society of Veterinary Science  2009
• (DBA/2 x C57BL/6) F2交雑マウスに出現する水腎症  [Not invited]

  市居 修, 昆 泰寛, 佐々木宣哉, 矢吹 映, 大塚沙織, 橋本善春, 遠藤大二

  第148回日本獣医学会学術集会  2009
• 腎疾患の新しい診断指標 −Interleukin 1 family, member 6は尿細管傷害マーカーになり得る  [Not invited]

  市居 修, 大塚沙織, 佐々木宣哉, 矢吹 映, 大田 寛, 滝口満喜, 橋本善春, 遠藤大二, 昆 泰寛

  第147回日本獣医学会学術集会  2009
• テンシン2遺伝子の糸球体上皮細胞における機能解析  [Not invited]

  佐々木宣哉, 市居 修, 昆 泰寛, 安居院高志

  第146回 日本獣医学術集会  2008/09
• The relations between autoimmune glomerulonephritis and Interferon activated gene 200 (Ifi200).  [Not invited]

  146th Meeting of the Japanease Society of Veterinary Science  2008
• The effects of gonadectomy on the pathogenesis of glomerulonephritis.  [Not invited]

  145th Meeting of the Japanease Society of Veterinary Science  2008
• Interferon activated gene 200 (Ifi200)遺伝子群と自己免疫性糸球体腎炎の関連性  [Not invited]

  市居修, 上川昭博, 佐々木宣哉, 今野明弘, 遠藤大二, 橋本善春, 昆 泰寛

  第146回日本獣医学会学術集会  2008
• 性腺摘出が自己免疫性糸球体腎炎の病態に与える影響について  [Not invited]

  市居 修, 今野明弘, 佐々木宣哉, 遠藤大二, 橋本善春, 昆 泰寛

  第145回日本獣医学会学術集会  2008
• The relations between autoimmune glomerulonephritis and Fc gamma receptor III（FcγRIII）.  [Not invited]

  144th Meeting of the Japanease Society of Veterinary Science  2007
• 自己免疫性糸球体腎炎と Fc gamma receptor III（FcγRIII）の関連性について  [Not invited]

  市居 修, 今野明弘, 佐々木宣哉, 遠藤大二, 橋本善春, 昆 泰寛

  第144回日本獣医学会学術集会  2007
• Autoimmune glomerulonephritis in MRL-derived congenic mice.  [Not invited]

  142th Meeting of the Japanease Society of Veterinary Science  2006
• MRL/MpJマウス由来コンジェニックマウスに出現する自己免疫性糸球体腎炎  [Not invited]

  市居 修, 今野明弘, 橋本善春, 昆 泰寛

  第142回日本獣医学会学術集会  2006
• Speciese-specific differences of laboratory redent kidenys- lenghts of nephrons, GFR associated factors, water channels and sodium pumps.  [Not invited]

  140th Meeting of the Japanease Society of Veterinary Science  2005
• 齧歯目の腎臓における種差―ネフロン長,GFR調節因子,水チャネルおよびナトリウムポンプについて  [Not invited]

  市居 修, 矢吹 映, 小嶋敏慶, 松元光春, 鈴木秀作

  第140回日本獣医学会学術集会  2005
• Speciese-specific differences of renal structures in laboratory animals.  [Not invited]

  22th Meeting of the Kyusyu Experimental Animal Research Association  2004
• 実験動物の腎臓の種差に関する形態計測学的研究  [Not invited]

  市居 修, 矢吹 映, 小嶋敏慶, 松元光春, 鈴木秀作

  第22回九州実験動物研究会総会  2004
• 雌性コットンラットの胸腺にみられる加齢性変化

  中村鉄平, 市居修, 入江隆夫, 篠原明男, 孝口裕一, 越本知大, 長崎健一, 寸田祐嗣, Yaser Hosny Ali Elewa, 辰巳治, 昆泰寛

  第160回日本獣医学会

MISC

• 【人工臓器開発に貢献するバイオマテリアル】動物iBTA組織のoff-the-shelfバイオマテリアルとしての可能性

  佐藤 康史, 岩井 良輔, 西邑 隆徳, 市居 修, 宮本 伸二, 秋吉 秀保, 中山 泰秀  人工臓器  48-  (3)  219  -222  2019/12  [Not refereed][Not invited]
  
• 自己免疫疾患モデルマウスにみられる涙液産生組織の形態学的変化

  平石 真也, 市居 修, 中村 鉄平, 難波 貴志, Hosny Ali Elewa Yaser, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  336  -336  2019/08  [Not refereed][Not invited]
  
• コットンラットの下咽頭梨状窩瘻を構成する細胞の組織化学的特徴

  中村 鉄平, 市居 修, 入江 隆夫, 寸田 祐嗣, 細谷 実里奈, 長崎 健一, Ali Elewa Yaser Hosny, 三嶋 隆, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  337  -337  2019/08  [Not refereed][Not invited]
  
• 自己免疫疾患モデルマウスで変化する腎臓内Interleukin 1 familyの発現バランス

  難波 貴志, 市居 修, 中村 鉄平, Ali Elewa Yaser Hosny, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  338  -338  2019/08  [Not refereed][Not invited]
  
• 動物の尿路関連リンパ組織(UTALT)に発現する分子群

  市居 修, 中村 鉄平, 堀野 太郎, 細谷 実里奈, Ali Elewa Yaser Hosny, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  338  -338  2019/08  [Not refereed][Not invited]
  
• 加齢マウスの尿生殖器における局所リンパ組織の探索

  山下 渚, 市居 修, 大谷 裕紀, Md. Abdul Md. Abdul, Hosny Ali Elewa Yaser, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  339  -339  2019/08  [Not refereed][Not invited]
  
• マウス生体内異物反応の経時観察 組織局所の炎症と線維化の関連性

  大江 紗央, 市居 修, 難波 貴志, 大谷 祐紀, Masum Md. Abdul, 中村 鉄平, Ali Elewa Yaser Hosny, 西邑 隆徳, 中山 泰秀, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  340  -340  2019/08  [Not refereed][Not invited]
  
• マウスの卵巣嚢-腹腔連絡路(卵巣嚢孔)

  細谷 実里奈, 市居 修, 中村 鉄平, 難波 貴志, Ali Elewa Yaser Hosny, 渡邉 敬文, 植田 弘美, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  340  -340  2019/08  [Not refereed][Not invited]
  
• 精巣摘出が自己免疫疾患モデルマウスの病態形成へ与える影響

  大谷 祐紀, 市居 修, Ali Elewa Yaser Hosny, 中村 鉄平, 昆 泰寛  日本獣医学会学術集会講演要旨集  162回-  341  -341  2019/08  [Not refereed][Not invited]
  
• ワクモ由来Adipocyte plasma membrane-associated proteinの抗ワクモワクチン抗原としての評価

  森田 鮎, 竹原 昌生, 村田 史郎, 伊勢崎 政美, 藤澤 宗太郎, 種子野 章, 酒井 英史, 宇野 有紀子, 小川 遼, 市居 修, 前川 直也, 岡川 朋弘, 今内 覚, 大橋 和彦  日本獣医学会学術集会講演要旨集  162回-  412  -412  2019/08  [Not refereed][Not invited]
  
• 慢性腎臓病の猫の腎臓におけるperoxisome proliferator activated receptor-γの発現動態

  矢吹 映, 上原 由季, 吉田 千紘, 市居 修, 大和 修  日本獣医学会学術集会講演要旨集  162回-  469  -469  2019/08  [Not refereed][Not invited]
  
• 詳細な病理学的解析に基づいて治療方針を決定した免疫複合体性糸球体腎炎の犬の1例

  新井田 篤, 大田 寛, 笹岡 一慶, 細谷 謙次, 市居 修, 賀川 由美子, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜  北海道獣医師会雑誌  63-  (8)  336  -336  2019/08  [Not refereed][Not invited]
  
• コットンラットの下咽頭梨状窩瘻を構成する細胞の組織化学的特徴

  中村鉄平, 中村鉄平, 市居修, 入江隆夫, 寸田祐嗣, 細谷実里奈, 長崎健一, YASER HOSNY, Ali Elewa, 三嶋隆, 昆泰寛  日本獣医学会学術集会講演要旨集  162回-  337  -337  2019/08  [Not refereed][Not invited]
  
• PCBs曝露によるネコ肝トランスクリプトームへの影響

  水川葉月, NGYUEN Hoa Thanh, 岩田久人, 野見山桂, 池中良徳, 中山翔太, 横山望, 市居修, 滝口満喜, KHIDKHAN Kraisiri, 田辺信介, 石塚真由美  環境化学討論会要旨集(CD-ROM)  28th-  ROMBUNNO.1C‐08  2019/06/11  [Not refereed][Not invited]
  
• デカブロモジフェニルエーテル(BDE209)の長期曝露がイエネコへ及ぼす影響

  田中啓介, 野見山桂, 水川葉月, 水川葉月, 高口倖暉, 田上瑠美, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介  環境化学討論会要旨集(CD-ROM)  28th-  ROMBUNNO.1C‐09  2019/06/11  [Not refereed][Not invited]
  
• 【マスト細胞研究の新展開】新生子MRL/MpJマウスにおいて卵巣マスト細胞は卵巣-卵巣采結合部の方向に遊走する 局在変化が明らかにするマスト細胞の新たな役割

  中村 鉄平, 市居 修, Elewa Yaser Hosny Ali, 昆 泰寛  臨床免疫・アレルギー科  71-  (6)  603  -607  2019/06  [Not refereed][Not invited]
  
• 生体内組織形成術を用いて作製したウシ由来バイオシートの性状に及ぼす生体内環境の影響

  今山 知佳, 寺澤 武, 中山 泰秀, 三谷 朋弘, 市居 修, 池田 哲平, 小千田 圭吾, 小林 謙, 鈴木 貴弘, 西邑 隆徳  日本畜産学会大会講演要旨集  125回-  172  -172  2019/03  [Not refereed][Not invited]
  
• 組織工学血管修復材(バイオシート)の開発 低圧系から高圧系、異種移植の可能性

  中山 泰秀, 古越 真耶, 今山 知佳, 市居 修, 西邑 隆徳  日本心臓血管外科学会学術総会抄録集  49回-  [PP  -236]  2019/02  [Not refereed][Not invited]
  
• iBTA心血管系修復再生材の開発 肺動脈、動脈パッチ移植の検討

  中山 泰秀, 古越 真耶, 今山 知佳, 市居 修, 西邑 隆徳  日本獣医麻酔外科学雑誌  49-  (Suppl.2)  252  -252  2018/12  [Not refereed][Not invited]
  
• iBTA僧帽弁の開発 リング付弁の検討

  中山 泰秀, 湯浅 啓史, 市居 修, 西邑 隆徳, 田地川 勉  日本獣医麻酔外科学雑誌  49-  (Suppl.2)  252  -252  2018/12  [Not refereed][Not invited]
  
• Tissue engineeringによる人工臓器作成 iBTA組織のoff-the-shelf人工臓器をめざして ウシバイオシートの異種移植

  中山 泰秀, 大島 奈公子, 巽 英介, 市居 修, 西邑 隆徳  人工臓器  47-  (2)  S  -17  2018/10  [Not refereed][Not invited]
  
• “Lymphoid tissues appearing in the urinary tract of animals (Urinary tract-associated lymphoid tissue, UTALT)”.

  O. Ichii, T. Nakamura, R. Ono, T. Horino, Y. H. A. Elewa, Y. Kon  The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan.  161th-  2018/09  [Not refereed][Not invited]
  
• “Morphological characteristics of the dromedary thyroid gland - and distribution of C cells”.

  T. Nakamura, O. Ichii, Y. H. A. Elewa, W. A. M. Ghonimi, K. Nagasaki, Y. Kon  The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan.  161th-  2018/09  [Not refereed][Not invited]
  
• “New findings of kidney disease - Kidney lesions found in Casp3 deficient mice”.

  T. Suzuki, O. Ichii, T. Nakamura, Y. H. A. Elewa, Y. Kon  The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan.  161th-  2018/09  [Not refereed][Not invited]
  
• “Morphological and functional changes observed in bone of autoimmune disease model”.

  T. Namba, O. Ichii, Y. H. A. Elewa, T. Nakamura, J. Kimura, Y. Otani, Md. A. Masum, Y. Kon  The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan.  161th-  2018/09  [Not refereed][Not invited]
  
• Investigation for meiotic apoptosis of spermatocyte in autoimmune disease model mouse.

  Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan.  161th-  2018/09  [Not refereed][Not invited]
  
• Effect of systemic autoimmune abnormality in MRL/MpJ-Faslpr/lpr mice on the ciliary function.

  M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 161th Meeting of the Japanese Society of Veterinary Sciences. Ibaraki, Tsukuba-shi, Japan  161th-  2018/09  [Not refereed][Not invited]
  
• “Mediastinal fat-associated lymphoid cluster and lung asthma development in papain induced lung asthma mice model

  Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon  The 64th annual meeting of the Japanese the Anatomical Society (Oral Presentation). Aomori, Japan.  64th-  2018/09  [Not refereed][Not invited]
  
• MRL/MpJ‐Fas^lpr/lprマウスの全身自己免疫異常が線毛運動機能に与える影響

  細谷実里奈, 市居修, ALI ELEWA, Yaser Hosny, 中村鉄平, 中村鉄平, 昆泰寛  日本獣医学会学術集会講演要旨集  161回-  296  -296  2018/08  [Not refereed][Not invited]
  
• 新たな腎病態マーカー分子の発見と臨床獣医学への応用に関する研究

  市居修  日本獣医学会学術集会講演要旨集  161回-  161  -161  2018/08  [Not refereed][Not invited]
  
• 動物の尿路に出現するリンパ組織(Urinary tractassociated lymphoid tissue,UTALT)

  市居修, 中村鉄平, 中村鉄平, 細谷実里奈, 堀野太郎, ALI ELEWA Yaser Hosny, 昆泰寛  日本獣医学会学術集会講演要旨集  161回-  294  -294  2018/08  [Not refereed][Not invited]
  
• 自己免疫疾患モデルマウスの骨に観察される形態機能的変化

  難波貴志, 市居修, 中村鉄平, 木村純平, 木村純平, 大谷祐紀, ABDUL Masum Md, HOSNY Ali Elewa Yaser, 昆泰寛  日本獣医学会学術集会講演要旨集  161回-  285  -285  2018/08  [Not refereed][Not invited]
  
• 腎疾患の新知見―Casp3欠損マウスにみられる腎病変―

  鈴木崇史, 市居修, 中村鉄平, 中村鉄平, ALI ELEWA Yaser Hosny, 昆泰寛  日本獣医学会学術集会講演要旨集  161回-  294  -294  2018/08  [Not refereed][Not invited]
  
• 自己免疫疾患モデルマウスで増加する減数分裂特異的精母細胞アポトーシスの原因探索

  大谷祐紀, 市居修, ALI ELEWA, Yaser Hosny, 木村純平, MASUM Md. Abdul, 中村鉄平, 中村鉄平, 昆泰寛  日本獣医学会学術集会講演要旨集  161回-  295  -295  2018/08  [Not refereed][Not invited]
  
• ウシの眼関連リンパ組織について

  小千田圭吾, 市居修, 中村鉄平, 中村鉄平, 池田哲平, 山下祐輔, 長澤裕哉, ALI ELEWA Yaser Hosny, 昆泰寛  日本獣医学会学術集会講演要旨集  161回-  288  -288  2018/08  [Not refereed][Not invited]
  
• ヒトコブラクダ甲状腺の形態学的特徴―鰓後体遺残とC細胞の分布―

  中村鉄平, 中村鉄平, 市居修, ALI ELEWA, Yaser Hosny, ALI ELEWA Yaser Hosny, 細谷実里奈, GHONIMI Wael A. M, 辰巳治, 長崎健一, 昆泰寛  日本獣医学会学術集会講演要旨集  161回-  292  -292  2018/08  [Not refereed][Not invited]
  
• “Glomerular lesions seen in male cotton rats (Sigmodon hispidus)”

  T. Nakamura, O. Ichii, T. Irie, H. Kouguchi, Sunden, Masum, M. A., Y, Y. H. A. Elewa, Y. Kon  The 11th Annual Meeting of the Japanese Society of Veterinary Renal Urology.  11th-  2018/08  [Not refereed][Not invited]
  
• ワクモ(Dermanyssus gallinae)由来カテプシンL用タンパク質の性状解析とワクチン抗原としての評価

  村田史郎, 伊勢崎政美, 谷口綾香, 北條巧, 種子野章, 酒井英史, 宇野有紀子, 矢吹卓也, 市居修, 伊東拓也, 今内覚, 大橋和彦  衛生動物  69-  (2)  103  -103  2018/06/25  [Not refereed][Not invited]
  
• 異種バイオシートの血管修復材への応用:肺動脈パッチモデルによる検討

  古越真耶, 古越真耶, 今山知佳, 市居修, 西邑隆徳, 中山泰秀, 中山泰秀  日本獣医麻酔外科学雑誌  49-  (Supplement 1)  272  -272  2018/06/05  [Not refereed][Not invited]
  
• Effects of PCB-exposure on thyroid hormone homeostasis in dog (canis lupus familiaris) and cat (felis catus)

  TAKAGUCHI Kohki, NAKAYAMA Shouta, IKENAKA Yoshinori, ISHIZUKA Mayumi, IWATA Hisato, KUNISUE Tatsuya, TANABE Shinsuke, NOMIYAMA Kei, NISHIKAWA Hiroyuki, MIZUKAWA Hazuki, TANOUE Rumi, KUSAKI Momoko, YOKOYAMA Nozomu, ICHII Osamu, TAKIGUCHI Mitsuyoshi  Annual Meeting of the Japanese Society of Toxicology  43-  (Suppl.)  S245  -S245  2018/06  [Not refereed][Not invited]
   

  [in Japanese]

• 異種バイオシートの血管修復材への応用 肺動脈パッチモデルによる検討

  古越 真耶, 今山 知佳, 市居 修, 西邑 隆徳, 中山 泰秀  日本獣医麻酔外科学雑誌  49-  (Suppl.1)  272  -272  2018/06  [Not refereed][Not invited]
  
• ワクモ(Dermanyssus gallinae)由来カテプシンL用タンパク質の性状解析とワクチン抗原としての評価

  村田 史郎, 伊勢崎 政美, 谷口 綾香, 北條 巧, 種子野 章, 酒井 英史, 宇野 有紀子, 矢吹 卓也, 市居 修, 伊東 拓也, 今内 覚, 大橋 和彦  衛生動物  69-  (2)  103  -103  2018/06  [Not refereed][Not invited]
  
• 有機ハロゲン化合物曝露によるネコの生化学マーカーの変化および甲状腺機能に及ぼす影響評価

  水川葉月, KHIDKHAN Kraisiri, 高口倖暉, 横山望, 市居修, 滝口満喜, 笹岡一慶, 池中良徳, 池中良徳, 中山翔太, TSEND‐AYUSH Sainnoxoi, 野見山桂, 田辺信介, 石塚真由美  環境化学討論会要旨集(CD-ROM)  27th-  ROMBUNNO.2A‐10  2018/05/11  [Not refereed][Not invited]
  
• ネコのin vivo BDE209長期曝露試験による体内動態の解明および甲状腺ホルモンへの影響評価

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介  環境化学討論会要旨集(CD-ROM)  27th-  ROMBUNNO.1A‐03(PA‐13)  2018/05/11  [Not refereed][Not invited]
  
• イヌ肺動脈に異種移植したウシ由来バイオシートの組織構造

  今山知佳, 鈴木貴弘, 小林謙, 三谷朋弘, 市居修, 中山泰秀, 古越真耶, 池田哲平, 小千田圭吾, 西邑隆徳  日本畜産学会大会講演要旨  124th-  115  -115  2018/03/28  [Not refereed][Not invited]
  
• イヌ肺動脈に異種移植したウシ由来バイオシートの組織構造

  今山 知佳, 鈴木 貴弘, 小林 謙, 三谷 朋弘, 市居 修, 中山 泰秀, 古越 真耶, 池田 哲平, 小千田 圭吾, 西邑 隆徳  日本畜産学会大会講演要旨集  124回-  115  -115  2018/03  [Not refereed][Not invited]
  
• Local CD34-positive capillary decreased with the progression of lesion in respective area of kidney in mice.

  Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 17th International Conference on Nephrology and Urology. London, UK. 13th March 2018.  17th-  2018/03  [Not refereed][Not invited]
  
• 肺動脈修復材としての異種結合組織膜バイオシートの開発

  古越真耶, 中山泰秀, 巽英介, 西邑隆徳, 市居修  日本心臓血管外科学会学術総会(Web)  48th-  ROMBUNNO.OP23‐1 (WEB ONLY)  -961  2018/02  [Not refereed][Not invited]
  
• 肺動脈修復材としての異種結合組織膜バイオシートの開発

  古越 真耶, 中山 泰秀, 巽 英介, 西邑 隆徳, 市居 修  日本心臓血管外科学会学術総会抄録集  48回-  960  -961  2018/02  [Not refereed][Not invited]
  
• 黄色ブドウ球菌性乳房炎における乳汁中乳腺上皮細胞の割合は乳腺組織の損傷を反映する

  長澤 裕哉, 菊 佳男, 菅原 和恵, 田邉 扶由子, 石川 義春, 市居 修, 野地 智法, 麻生 久, 昆 泰寛, 門田 耕一, 林 智人  家畜感染症学会誌  6-  (4)  165  -165  2017/12  [Not refereed][Not invited]
  
• ポリ塩化ビフェニル(PCBs)がネコの甲状腺機能に及ぼす影響

  水川 葉月, 高居 名菜, 野見山 桂, 高口 倖暉, 横山 望, 市居 修, 滝口 満喜, 池中 良徳, 中山 翔太, 石塚 真由美  環境ホルモン学会研究発表会要旨集  20回-  78  -78  2017/12  [Not refereed][Not invited]
  
• ポリ塩化ビフェニル(PCBs)がネコの甲状腺機能に及ぼす影響

  水川葉月, 高居名菜, 野見山桂, 高口倖暉, 横山望, 市居修, 滝口満喜, 池中良徳, 池中良徳, 中山翔太, 石塚真由美  日本内分泌かく乱化学物質学会研究発表会要旨集  20th-  78  -78  2017/12  [Not refereed][Not invited]
  
• BXSB/MpJ-Yaa MICE SHOW THE INCREASE OF APOPTOTIC SPERMATOCYTES IN STAGE Ⅻ SEMINIFEROUS TUBULES.

  Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 6th Congress of Asian Association of Veterinary Anatomists (Asian AVA). Kuching, Sarawak, Malaysia. October 12-13, 2017.  6th-  2017/10  [Not refereed][Not invited]
  
• ABNOLMALITY OF OVULATION AND OOCYTE-PICK-UP IN MRL/MpJ-Faslpr/lpr MICE.

  Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, S. Otsuka-Kanazawa, Y. Kon  ABNOLMALITY OF OVULATION AND OOCYTE-PICK-UP IN MRL/MpJ-Faslpr/lpr MICE. The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia  6th-  2017/10  [Not refereed][Not invited]
  
• IL-1F6/IL-36α SIGNALING REGULATES RENAL INFLAMMATION.

  O. Ichii, J. Kimura, T. Okamura, T. Horino, T. Nakamura, H. Sasaki, H. A. Elewa, Y. Kon  The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia  6th-  2017/10  [Not refereed][Not invited]
  
• FAT ACCUMULATION CORRELATES WITH DIABETES MELLITUS IN MALE COTTON RATS (SIGMODON HISPIDUS).

  T. Nakamura, O. Ichii, T. Irie, H. Kouguchi, Y. Sunden, K.-I. Nagasaki, Y. H. A. Elewa, Y. Kon  The 6th Congress of Asian Association of Veterinary Anatomists, Malaysia  2017/10  [Not refereed][Not invited]
  
• 鳥類医学の発展に向けた新規腎障害マーカーの探索

  石井千尋, 池中良徳, 川合佑典, 市居修, 中山翔太, 水川葉月, 石塚真由美  日本鳥学会大会講演要旨集  2017-  100  2017/09/15  [Not refereed][Not invited]
  
• “Mechanism and abnormality of ovulation and picking up of mammalian oocytes-Immune factors affecting the molecular morphology of the oviduct.”

  M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 5th Sapporo Summer Seminar for One Health (SASSOH). September 20-21, 2017. Sapporo, Japan.  5th-  2017/09  [Not refereed][Not invited]
  
• “Loss of endothelial fenestration correlates with podocyte injury in the mouse model of membranoproliferative glomerulonephritis.”

  Md. A. Masum, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 5th Sapporo Summer Seminar for One Health (SASSOH). September 20-21, 2017. Sapporo, Japan.  5th-  2017/09  [Not refereed][Not invited]
  
• “The unique phenotype in ovulation and corpus luteum formation in MRL/MpJ mouse.”

  M. Hosotani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 160th Meeting of the Japanese Society of Veterinary Sciences, September 13-16, 2017. Kagoshima, Japan.  160th-  2017/09  [Not refereed][Not invited]
  
• Histopathological features observed in the testis of autoimmune-prone BXSB/MpJ-Yaa mice.

  Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 5th Sapporo Summer Seminar for One Health.  5th-  2017/09  [Not refereed][Not invited]
  
• Apoptosis of spermatocytes seen in BXSB / MpJ-Yaa mice - association with autoimmune abnormality.

  Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura, Y. Kon  The 160th Meeting of the Japanese Society of Veterinary Sciences.  160th-  2017/09  [Not refereed][Not invited]
  
• “Dual effects of bleomycin on the intra-thoracic immune hemostasis and lung injury in autoimmune disease model mice”.

  Y. H. A. Elewa, T. Nakamura, O. Ichii, Y. Kon  The 63th annual meeting of the Japanese the Anatomical Society.  63th-  2017/09  [Not refereed][Not invited]
  
• マウス糸球体の自己免疫関連傷害における内皮細胞と有足細胞との病理学的相関性(Pathological correlations between endothelial cells and podocytes in autoimmune-related injury of the mouse glomerulus)

  Masum Md. Abdul, 市居 修, Elewa Yaser Hosny Ali, 中村 鉄平, 昆 泰寛  日本獣医学会学術集会講演要旨集  160回-  310  -310  2017/08  [Not refereed][Not invited]
  
• Elucidation of mammalian reproductive - autoimmune coupling mechanism and analysis of pathological conditions caused by its failure.

  Y. Otani, O. Ichii, Y. H. A. Elewa, T. Nakamura  Y. Kon. The 35th Scientific annual joint meeting of Hokkaido Veterinary Anatomy  35th-  2017/08  [Not refereed][Not invited]
  
• Caspase3欠損マウスからみる細胞死―自己免疫連関異常の新たなエビデンス

  市居修, 堀野太郎, 大田寛, 鈴木崇史, 中村鉄平, 中村鉄平, ELEWA Yaser, Hosny Ali, 昆泰寛  日本獣医学会学術集会講演要旨集  160回-  310  -310  2017/08  [Not refereed][Not invited]
  
• Sarcocystis属原虫の終宿主候補としてのキタキツネにおける調査

  入江隆夫, 浦口宏二, 中村鉄平, 中村鉄平, 市居修, 高井伸二, 八木欣平  日本獣医学会学術集会講演要旨集  160回-  335  -335  2017/08  [Not refereed][Not invited]
  
• 犬と猫の慢性腎臓病における腎臓へのマクロファージ浸潤

  大原優美子, 矢吹映, 市居修, 水川葉月, 横山望, 中村麗菜  日本獣医学会学術集会講演要旨集  160回-  473  -473  2017/08  [Not refereed][Not invited]
  
• BXSB/MpJ‐Yaaマウスにみられる精母細胞のアポトーシス―自己免疫異常との関連性―

  大谷祐紀, 市居修, ELEWA Yaser, Hosny Ali, 木村純平, MASUM Md. Abdul, 中村鉄平, 中村鉄平, 昆泰寛  日本獣医学会学術集会講演要旨集  160回-  312  -312  2017/08  [Not refereed][Not invited]
  
• 雌性コットンラットの胸腺にみられる加齢性変化

  中村鉄平, 中村鉄平, 市居修, 入江隆夫, 篠原明雄, 孝口裕一, 越本知大, 長崎健一, 寸田祐嗣, ELEWA Yaser Hosny, 辰巳治, 昆泰寛  日本獣医学会学術集会講演要旨集  160回-  309  -309  2017/08  [Not refereed][Not invited]
  
• MRL/MpJマウスの排卵―黄体形成過程にみられる特異な表現型

  細谷実里奈, 市居修, ELEWA Yaser, Hosny Ali, 中村鉄平, 中村鉄平, 昆泰寛  日本獣医学会学術集会講演要旨集  160回-  313  -313  2017/08  [Not refereed][Not invited]
  
• 過去の報告とは異なる受傷機転で生じた鎖骨遠位端骨折(Rockwood分類type6)の治療経験

  須賀 佑磨, 奥田 亮宏, 市居 幸彦, 平岡 修治, 芳谷 和洋, 吉田 淳, 前川 尚宜, 田中 康仁  骨折  39-  (Suppl.)  S402  -S402  2017/07  [Not refereed][Not invited]
  
• ポリ塩化ビフェニル(PCBs)暴露によるネコ甲状腺機能への影響評価~甲状腺ホルモンの脱ヨード化と代謝能の解析~

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 池中良徳, 中山翔太, SAINNOXOI Tsend‐ayush, 田辺信介, 石塚真由美  環境化学討論会要旨集(CD-ROM)  26th-  ROMBUNNO.2A‐01  2017/06/05  [Not refereed][Not invited]
  
• PCBs曝露がイヌ・ネコの甲状腺ホルモン恒常性へ及ぼす影響

  高口倖暉, 野見山桂, 西川博之, 水川葉月, 田上瑠美, 芳之内結加, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 岩田久人, 国末達也, 田辺信介  環境化学討論会要旨集(CD-ROM)  26th-  ROMBUNNO.2A‐02  2017/06/05  [Not refereed][Not invited]
  
• イエネコのin vivo長期曝露試験:デカブロモジフェニルエーテル(BDE209)は甲状腺機能亢進症を引き起こすのか?

  水川葉月, 野見山桂, 池中良徳, 池中良徳, 中山翔太, SAENGTIENCHAI Aksorn, SAINNOXOI Tsendayush, 横山望, 笹岡一慶, 市居修, KHIDKHAN Kraisiri, 高居名菜, 滝口満喜, 田辺信介, 石塚真由美  環境化学討論会要旨集(CD-ROM)  26th-  ROMBUNNO.2A‐03  2017/06/05  [Not refereed][Not invited]
  
• 血清中メタボローム解析によるイエネコのPCBs毒性影響評価

  野見山桂, 西川博之, 水川葉月, 高口倖暉, SAINNOXOI Tsend‐ayush, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介  環境化学討論会要旨集(CD-ROM)  26th-  ROMBUNNO.2A‐05  2017/06/05  [Not refereed][Not invited]
  
• イエネコのin vivo長期曝露試験:デカブロモジフェニルエーテル(BDE209)の生体内変化

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, SAENGTIENCHAI Aksorn, SAINNOXOI Tsend‐ayush, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介  環境化学討論会要旨集(CD-ROM)  26th-  ROMBUNNO.2A‐04  2017/06/05  [Not refereed][Not invited]
  
• ネコの甲状腺機能に対するポリ塩化ビフェニル(PCBs)の影響評価~甲状腺ホルモンの脱ヨード化と代謝能の解析~

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 池中良徳, 中山翔太, SAINNOXOI Tsend‐Ayush, 田辺信介, 石塚真由美  Journal of Toxicological Sciences  42-  (Suppl.)  S236  -S236  2017/06  [Not refereed][Not invited]
  
• ウシ生体内で形成させた移植医療用組織の構造

  今山知佳, 鈴木貴弘, 小林謙, 三谷朋弘, 市居修, 小千田圭吾, 池田哲平, 寺澤武, 中山泰秀, 西邑隆徳  日本畜産学会大会講演要旨  122回-  175  -175  2017/03  [Not refereed][Not invited]
  
• 家畜生体内で再生医療移植用組織をつくる

  西邑隆徳, 今山知佳, 鈴木貴弘, 小林謙, 三谷朋弘, 市居修, 小千田圭吾, 池田哲平, 寺澤武, 中山泰秀  日本畜産学会大会講演要旨  122回-  175  -175  2017/03  [Not refereed][Not invited]
  
• 生体内組織形成術による組織厚制御の可能性:管状組織体の作製

  寺澤武, 寺澤武, 西邑隆徳, 三谷朋弘, 市居修, 中山泰秀, 中山泰秀  再生医療  16-  336  2017/02/01  [Not refereed][Not invited]
  
• MicroRNA研究の実際と問題点 腎臓病を知らせるmicroRNA 病態マーカーとしての可能性と問題点

  市居 修  日本毒性病理学会講演要旨集  33回-  52  -52  2017/01  [Not refereed][Not invited]
  
• Thyroid hormone effects of polychlorinated biphenyls (PCBs) in cats-Analysis of deiodination and metabolism-

  MIZUKAWA Hazuki, NAKAYAMA Shouta M.M., SAINNOXOI Tsend-ayush, TANABE Shinsuke, ISHIZUKA Mayumi, TAKAI Nana, YOKOYAMA Nozomu, ICHII Osamu, TAKIGUCHI Mitsuyoshi, NOMIYAMA Kei, TAKAGUCHI Kohki, NISHIKAWA Hiroyuki, IKENAKA Yoshinori  Annual Meeting of the Japanese Society of Toxicology  44-  (0)  P  -55  2017  [Not refereed][Not invited]
   

  有機ハロゲン化合物の一種であるポリ塩化ビフェニル（PCBs）は甲状腺ホルモン（THs）の恒常性かく乱が懸念されており、実際、ヒトやげっ歯類においてはPCBs暴露により血中THs濃度の低下が認められている。ヒトの身近な動物であるネコは餌などを介してPCBsに暴露していると懸念され、THs恒常性に何らかの悪影響をもたらすことが予想される。本研究では、ネコの甲状腺機能に対するPCBsの影響を解析するため、<i>in vivo</i>投与試験したネコを用いて甲状腺機能への影響を解析した。血中のTHs濃度（総T4、総T3、遊離T4、遊離T3、リバースT3）を解析した結果、対照群と暴露群の間に有意な差は見られなかった。また、THsの恒常性に関与する遺伝子（甲状腺ホルモン受容体αおよびβ、脱ヨード酵素type1）の肝臓中発現量やTHs代謝に関わる酵素であるグルクロン酸抱合酵素（UGT1A1）の活性を調べたところ、対照群と暴露群の間に有意な差は見られなかった。<br>本実験結果では、ネコにおいてPCBs短期暴露によるTHsへの影響が認められなかったが、日本のペットネコにおけるモニタリング調査では、血中のTHs濃度とPCBs濃度との間に負の相関が見られており、有機ハロゲン化合物によるTHsかく乱が懸念されている。また、本研究試料のメタボローム解析結果では酸化ストレスの発現、抗酸化物質、電子伝達物質の生産阻害などが示唆されており、PCBsや水酸化代謝物による内分泌撹乱作用が心配される。THsの恒常性は非常に複雑な機構のもと維持されていることが知られており、負のフィードバック機構に加え、THsの活性化や代謝、排泄の調整にも多くの遺伝子やトランスポーター、酵素など様々な要因が関わっていることから、ネコは長期的かつ慢性的に化学物質に暴露されることで、甲状腺機能などへの悪影響が現れると考えられ、内分泌撹乱作用の作用機序について解析を進めることが重要である。
• 腎臓病を知らせるmicroRNA―病態マーカーとしての可能性と問題点―

  市居修  日本毒性病理学会講演要旨集  33rd-  52 (JA),154 (EN)  2017  [Not refereed][Not invited]
  
• 黄色ブドウ球菌性乳房炎における乳汁中乳腺上皮細胞の割合は乳腺組織の損傷を反映する

  長澤 裕哉, 菊 佳男, 菅原 和恵, 田邉 扶由子, 石川 義春, 市居 修, 野地 智法, 麻生 久, 昆 泰寛, 門田 耕一, 林 智人  家畜感染症学会誌  5-  (4)  180  -180  2016/12  [Not refereed][Not invited]
  
• 生体内組織形成術による管状組織体の壁厚制御

  寺澤武, 寺澤武, 西邑隆徳, 三谷朋弘, 市居修, 中山泰秀, 中山泰秀  人工臓器(日本人工臓器学会)  45-  (2)  S.129  -129  2016/10/31  [Not refereed][Not invited]
  
• 生体内組織形成術による管状組織体の壁厚制御

  寺澤 武, 西邑 隆徳, 三谷 朋弘, 市居 修, 中山 泰秀  人工臓器  45-  (2)  S  -129  2016/10  [Not refereed][Not invited]
  
• X線照射はミトコンドリア生合成を亢進することなく細胞内ミトコンドリア含量を増大させる

  山盛徹, 笹川朋哉, 市居修, 房知輝, 昆泰寛, 稲波修  日本放射線影響学会大会抄録(Web)  59回-  13  -13  2016/10  [Not refereed][Not invited]
  
• 自己免疫疾患モデルMRL/MpJ‐Fas^lprマウスにみられる卵子のキャッチアップ障害

  細谷実里奈, 中村鉄平, 中村鉄平, HOSNY Ali Elewa Yaser, HOSNY Ali Elewa Yaser, 市居修, 昆泰寛  日本獣医学会学術集会講演要旨集  159th-  314  2016/08/30  [Not refereed][Not invited]
  
• マウスにおける縦隔脂肪関連リンパクラスターとブレオマイシン誘発性肺炎との病理組織学的関連(Histopathological correlations between the mediastinal fat associated lymphoid clusters and bleomycin-induced pneumonitis in mice)

  Ali Elewa Yaser Hosny, Masum Md.Abdul, 中村 鉄平, 市居 修, 昆 泰寛  日本獣医学会学術集会講演要旨集  159回-  302  -302  2016/08  [Not refereed][Not invited]
  
• マウス腎臓病モデルにおける疾患進行に伴うCD34陽性毛細血管の減少(CD34-positive capillary decreased with the progression of kidney disease in mouse models)

  Masum Md.Abdul, Yaser Hosny Ali Elewa, 中村 鉄平, 市居 修, 昆 泰寛  日本獣医学会学術集会講演要旨集  159回-  308  -308  2016/08  [Not refereed][Not invited]
  
• “Histopathological evaluation of the possible protective role of royal jelly and cod liver oil against reproductive toxicity of tartrazine in adult male albino rats.”

  Y. H. A. Elewa, A. Moustafa, A.A. Mohamed, A. A.A. Galal, O. Ichii, Y. Kon  The 8th international Toxicology symposium in Africa. Cairo, Egypt.  8th-  2016/08  [Not refereed][Not invited]
  
• エゾシカに寄生するSarcocystis属原虫の終宿主動物探索

  入江隆夫, 池田徹也, 中村鉄平, 中村鉄平, 市居修, 山田智子, 伊東拓也, 山崎朗子, 高井伸二, 八木欣平  日本獣医学会学術集会講演要旨集  159回-  338  -338  2016/08  [Not refereed][Not invited]
  
• ウシ咽頭扁桃は鼻腔投与した黄色ブドウ球菌死菌に対する免疫応答の場になる

  長澤裕哉, 菊佳男, 菅原和恵, 田邉扶由子, 石川義春, 野地智法, 市居修, 昆泰寛, 麻生久, 門田耕一, 林智人  日本獣医学会学術集会講演要旨集  159回-  362  -362  2016/08  [Not refereed][Not invited]
  
• 芳香族炭化水素受容体シグナルの活性化は胃粘膜異常を増悪する―遺伝子改変モデルマウスを用いたin vivo解析―

  團塚愛, HANBERG Annika, 中村鉄平, 中村鉄平, 市居修, 昆泰寛  日本獣医学会学術集会講演要旨集  159回-  314  -314  2016/08  [Not refereed][Not invited]
  
• コットンラットにおけるインスリン抵抗性と脂肪蓄積との関連

  中村鉄平, 中村鉄平, 市居修, 入江隆夫, 寸田祐嗣, 孝口裕一, 長崎健一, 吉安友二, 昆泰寛  日本獣医学会学術集会講演要旨集  159回-  304  -304  2016/08  [Not refereed][Not invited]
  
• 自己免疫疾患モデルMRL/MpJ-Faslprマウスにみられる卵子のキャッチアップ障害

  細谷 実里奈, 中村 鉄平, Hosny Ali Elewa Yaser, 市居 修, 昆 泰寛  日本獣医学会学術集会講演要旨集  159回-  314  -314  2016/08  [Not refereed][Not invited]
  
• 鶏胸大動脈におけるグロムス細胞からの5-HT放出に対するH2Sの作用(Effect of H2S on 5-HT release from glomus cells in the chicken thoracic aorta)

  Delgermurun Dugar, 山口 聡一郎, 市居 修, 昆 泰寛, 伊藤 茂男, 乙黒 兼一  日本獣医学会学術集会講演要旨集  159回-  495  -495  2016/08  [Not refereed][Not invited]
  
• マウス遠位尿細管の嚢胞形成に関与する新規原因遺伝子座の役割

  市居修, 中村鉄平, 中村鉄平, 矢吹映, 堀野太郎, 昆泰寛  日本獣医学会学術集会講演要旨集  159回-  308  -308  2016/08  [Not refereed][Not invited]
  
• マウス胎子腸管器官培養法により形成された十二指腸空腸曲の解析

  尾之内佐和, 市居修, 昆泰寛  日本獣医学会学術集会講演要旨集  159回-  302  -302  2016/08  [Not refereed][Not invited]
  
• 抗ワクモ(Dermanyssus gallinae)ワクチン開発に向けたワクモ由来フェリチン2の性状解析

  伊勢崎政美, 村田史郎, 酒井英史, 矢吹卓也, 種子野章, 市居修, 伊東拓也, 今内覚, 大橋和彦  日本獣医学会学術集会講演要旨集  159回-  399  -399  2016/08  [Not refereed][Not invited]
  
• 犬と猫の慢性腎臓病における尿細管周囲毛細血管の変化

  中村麗菜, 矢吹映, 市居修, 水川葉月, 横山望, 大和修  日本獣医学会学術集会講演要旨集  159回-  462  -462  2016/08  [Not refereed][Not invited]
  
• メタボローム解析を用いたイエネコにおけるPCBsの毒性影響評価

  西川博之, 野見山桂, 水川葉月, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介  環境化学討論会要旨集(CD-ROM)  25th-  ROMBUNNO.1A‐12  2016/06/06  [Not refereed][Not invited]
  
• ネコにおけるポリ塩化ビフェニル(PCBs)の異物代謝機構解明と甲状腺ホルモンへの影響評価

  水川葉月, 前原美咲, 横山望, 市居修, 滝口満喜, 野見山桂, 西川博之, 池中良徳, 中山翔太, 高口倖暉, 田辺信介, 石塚真由美  環境化学討論会要旨集(CD-ROM)  25th-  ROMBUNNO.1A‐13  2016/06/06  [Not refereed][Not invited]
  
• In vivo analysis of metabolic capacities and effects on the thyroid hormone and in cats treated with polychlorinated biphenyls

  MIZUKAWA Hazuki, TAKAGUCHI Kohki, TANABE Shinsuke, ISHIZUKA Mayumi, MAEHARA Misaki, YOKOYAMA Nozomu, ICHII Osamu, TAKIGUCHI Mitsuyoshi, NOMIYAMA Kei, NISHIKAWA Hiroyuki, IKENAKA Yoshinori, NAKAYAMA Shouta M.M.  Annual Meeting of the Japanese Society of Toxicology  41-  (Suppl.)  S215  -S215  2016/06  [Not refereed][Not invited]
   

  ポリ塩化ビフェニル（PCBs）の水酸化代謝物であるOH-PCBsは、肝臓内で薬物代謝酵素より生成され、その後体外へ排泄される。しかしながら、一部の水酸化代謝物は甲状腺ホルモン（TH）と類似の構造をもつため、THの恒常性を撹乱することが危惧されている。これまでに、多様な陸棲哺乳類の血中OH-PCBsを分析したところ、種間でOH-PCBsの組成に差異が認められ、中でも、ネコのOH-PCBs残留パターンは他種と大きく異なることから、本種は特異な代謝機能を有することが示唆された。しかし、ネコの異物代謝能の研究は僅かであり、化学物質暴露による毒性影響も不明な点が多い。本研究では、ネコにおけるPCBs <i>in vivo</i>暴露試験を実施し、体内動態および代謝に関与する酵素活性や遺伝子を解析するとともに、化学物質の暴露評価に繋がる基盤的情報の収集を目的とした。<br>コーン油に溶解した12異性体のPCBsを腹腔内投与し、経時採血した血清中PCBsおよびOH-PCBs濃度について同条件で実施したイヌの<i>in vivo</i>試験と比較した結果、異性体の残留パターンや体内動態にイヌとネコで種差が観察された。とくにネコでは低塩素化体の残留が顕著であった。また、代謝酵素活性および遺伝子解析の結果、PCBs暴露によりEROD、MROD、PROD活性は上昇するものの、第2相抱合酵素（UGTやSULT）活性は変化せず、PCBs暴露による抱合酵素活性への影響もみられなかった。また、<i>CYP1A1</i>および<i>CYP1A2</i>遺伝子の発現量の上昇も認められた。<br> 本研究により、ネコのPCBs吸収・代謝・排泄能はイヌと異なることが示唆され、とくに低塩素化OH-PCBsの毒性リスクは高いことが予想された。低塩素化OH-PCBsは血中でTH輸送タンパクとの競合結合や、THの硫酸抱合排泄の阻害、TH起因性遺伝子の転写抑制などが報告されており、ネコの甲状腺機能障害が懸念される。
• 3D‐SEM法を利用した腎生検の迅速電子顕微鏡診断への応用

  高木孝士, 城謙輔, 大野伸彦, 大野伸彦, 齊藤成, THAI Quynh T, 昆泰寛, 市居修, YESER Alewa H, 笹野公伸  日本病理学会会誌  105-  (1)  369  -369  2016/04  [Not refereed][Not invited]
  
• “Sex-related difference of the mediastinal fat associated lymphoid clusters in MRL/MpJ-Faslpr autoimmune disease model mice.”

  Y. H. A. Elewa, O. Ichii, Y. Kon  The 11th Scientific Vet. Med. (second international) conference. El-Ain-El Sokhna, Egypt.  11th-  2016/03  [Not refereed][Not invited]
  
• Rapid specimen preparation to improve throughput of electron microscopic volume imaging

  THAI Truc Quynh, NGUYEN Huy Bang, SAITOH Sei, SAITOH Yurika, SHIMO Satoshi, ELEWA Yaser, Hosny Ali, ICHII Osamu, KON Yasuhiro, TAKAKI Takashi, JOH Kensuke, OHNO Nobuhiko  日本顕微鏡学会関東支部講演会予稿集  40th-  26  2016  [Not refereed][Not invited]
  
• 鳥類における新規腎障害マーカーの探索

  石井千尋, 池中良徳, 市居修, 中山翔太, 西村紳一郎, 大橋哲, 田中誠一, 齊藤慶輔, 渡邊有希子, 水川葉月, 石塚真由美  日本野生動物医学会大会・講演要旨集  22nd-  123  2016  [Not refereed][Not invited]
  
• ケージ交換時のハンドリングは実験用マウスの表現型に影響を与えるか?

  小野麻衣子, 佐々木隼人, 長崎健一, 鳥越大輔, 市居修, 佐々木宣哉, 安居院高志  日本実験動物技術者協会総会講演要旨集  49th-  59  2015/09/03  [Not refereed][Not invited]
  
• デノスマブ(60mg)投与後の血圧変動について

  城崎 和久, 奥田 亮宏, 市居 幸彦, 平岡 修治, 芳谷 和洋, 須賀 佑磨, 田中 康仁  Osteoporosis Japan  23-  (Suppl.1)  261  -261  2015/08  [Not refereed][Not invited]
  
• 腰椎椎弓切除既往患者の椎体骨折に対して、体幹ギプス固定とテリパラチド20μg連日製剤投与による保存療法が奏効した一例

  須賀 佑磨, 城崎 和久, 奥田 亮宏, 市居 幸彦, 平岡 修治, 芳谷 和洋, 田中 康仁  Osteoporosis Japan  23-  (Suppl.1)  357  -357  2015/08  [Not refereed][Not invited]
  
• マウス十二指腸空腸曲の細胞外基質は屈曲形成と共に変遷する

  尾之内佐和, 市居修, 昆泰寛  日本獣医学会学術集会講演要旨集  158回-  277  -277  2015/08  [Not refereed][Not invited]
  
• 遠位尿細管傷害を知らせるマーカー分子“IL‐1F6/IL‐36a”の有用性

  市居修, 中村鉄平, 中村鉄平, 堀野太郎, 木村純平, 岡村匡史, 昆泰寛  日本獣医学会学術集会講演要旨集  158回-  276  -276  2015/08  [Not refereed][Not invited]
  
• ミニチュア・ダックスフンドの炎症性結直腸ポリープ症例の結直腸粘膜におけるToll‐like receptor2,4の局在解析

  横山望, 大田寛, 賀川由美子, 山崎淳平, 市居修, KHOIRUN Nisa, 森田智也, 大菅辰幸, 佐々木東, 森下啓太郎, 中村健介, 滝口満喜  日本獣医学会学術集会講演要旨集  158回-  402  -402  2015/08  [Not refereed][Not invited]
  
• コットンラットの咽頭喉頭部,甲状腺及びその周囲組織にみられる形態異常

  中村鉄平, 中村鉄平, 入江隆夫, 市居修, 篠原明夫, 浦口宏二, 越本知大, 長崎健一, 昆泰寛  日本獣医学会学術集会講演要旨集  158回-  274  -274  2015/08  [Not refereed][Not invited]
  
• A Novel Mouse Mediastinal Fat-associated Lymphoid Tissue and Its Relationship with Autoimmune Disease

  Y. H. A. Elewa, O. Ichii, S. Otsuka-Kanazaw, Y. Kon  The 5th Congress of Asian Association of Veterinary Anatomists (Asian AVA). Bali, Indonesia  5th-  2015/02  [Not refereed][Not invited]
  
• miR‐26a―腎糸球体上皮細胞の機能形態を制御する短鎖RNA

  市居修  日本獣医学会学術集会講演要旨集  157th-  217  2014/08/11  [Not refereed][Not invited]
  
• 細胞形態ダイナミクスをリードする分子群を求めて miR-26a 腎糸球体上皮細胞の機能形態を制御する短鎖RNA

  市居 修  日本獣医学会学術集会講演要旨集  157回-  217  -217  2014/08  [Not refereed][Not invited]
  
• 新生子MRL/MpJマウスにおける卵巣内肥満細胞の由来 卵巣-卵素采結合部から出現する可能性

  中村 鉄平, 千原 正尚, 市居 修, 大塚 沙織, 長崎 健一, 昆 泰寛  日本獣医学会学術集会講演要旨集  157回-  320  -320  2014/08  [Not refereed][Not invited]
  
• マウス縦隔の脂肪関連リンパ球集積の性状解析(Characterization of mouse mediastinal fat-associated lymphoid clusters)

  Elewa Yaser Hosny Ali, 市居 修, 大塚 沙織, 昆 泰寛  日本獣医学会学術集会講演要旨集  157回-  330  -330  2014/08  [Not refereed][Not invited]
  
• Greb1―DBA/2Crマウスに出現する遠位尿細管由来嚢胞の原因遺伝子候補―

  市居修, 大塚沙織, 矢吹映, 堀野太郎, 中村鉄平, 昆泰寛  日本獣医学会学術集会講演要旨集  157回-  328  -328  2014/08  [Not refereed][Not invited]
  
• Toll‐like receptor 8は自己免疫性糸球体腎炎の足細胞傷害に関与する

  木村純平, 市居修, 大田寛, 中村鉄平, 堀野太郎, 大塚沙織, 昆泰寛  日本獣医学会学術集会講演要旨集  157回-  323  -323  2014/08  [Not refereed][Not invited]
  
• 自己免疫疾患モデルMRL/MpJ‐lprマウスの卵巣は機能形態異常を示す

  大谷祐紀, 市居修, 大塚沙織, 中村鉄平, 千原正尚, 昆泰寛  日本獣医学会学術集会講演要旨集  157回-  326  -326  2014/08  [Not refereed][Not invited]
  
• マウス十二指腸空腸曲における屈曲内‐外側の形態学的差異

  尾之内佐和, 市居修, 大塚沙織, 昆泰寛  日本獣医学会学術集会講演要旨集  157回-  325  -325  2014/08  [Not refereed][Not invited]
  
• MRL/MpJマウスに出現する精巣内卵細胞のエピゲノム解析

  大塚沙織, 市居修, 昆泰寛  日本獣医学会学術集会講演要旨集  157回-  319  -319  2014/08  [Not refereed][Not invited]
  
• 新生子MRL/MpJマウスにおける卵巣内肥満細胞の由来―卵巣‐卵巣采結合部から出現する可能性―

  中村鉄平, 千原正尚, 市居修, 大塚沙織, 長崎健一, 昆泰寛  日本獣医学会学術集会講演要旨集  157回-  320  -320  2014/08  [Not refereed][Not invited]
  
• 腎障害時にみられるMRL/MpJマウスの特別な修復過程について

  塩水流大地, 市居修, 中村鉄平, 大塚沙織, 昆泰寛  日本獣医学会学術集会講演要旨集  157回-  324  -324  2014/08  [Not refereed][Not invited]
  
• 低Ca血症を合併した重症骨粗鬆症にテリパラチド連日製剤とデノスマブを組み合わせた治療経験

  城崎 和久, 奥田 亮宏, 市居 幸彦, 平岡 修治, 芳谷 和洋, 田中 康仁  Osteoporosis Japan  21-  (Suppl.1)  278  -278  2013/09  [Not refereed][Not invited]
  
• ビタミンA欠乏食給餌マウスからみる精細胞‐血液精巣関門の相互作用

  千原正尚, 市居修, 大塚沙織, 昆泰寛  日本獣医学会学術集会講演要旨集  156回-  200  -200  2013/08  [Not refereed][Not invited]
  
• マウス慢性膵炎の系統差に関する研究―MRLマウス1番染色体テロメア領域の影響―

  岡田祐樹, 市居修, 大塚沙織, 昆泰寛  日本獣医学会学術集会講演要旨集  156回-  195  -195  2013/08  [Not refereed][Not invited]
  
• MRL/MpJマウスの卵細胞発育を制御する遺伝学的因子

  山下由真, 市居修, 大塚沙織, 昆泰寛  日本獣医学会学術集会講演要旨集  156回-  198  -198  2013/08  [Not refereed][Not invited]
  
• 伴侶動物の腎臓に発現するmiRNAのデータベース構築―動物種共通のバイオマーカー開発を目指して―

  市居修, 大塚沙織, 矢吹映, 大田寛, 堀野太郎, 昆泰寛  日本獣医学会学術集会講演要旨集  156回-  193  -193  2013/08  [Not refereed][Not invited]
  
• Ovarian cysts in MRL/MpJ mice are derived from the extraovarian rete: a developmental study (vol 219, pg 743, 2011)

  Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yaser Hosny Ali Elewa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon  JOURNAL OF ANATOMY  222-  (3)  396  -396  2013/03  [Not refereed][Not invited]
  
• 糸球体病変を制御するmiRNAの探索―動物種共通のバイオマーカー開発を目指して―

  市居修, 大塚沙織, 中村鉄平, 野元由佳, 橋本善春, 堀野太郎, 昆泰寛  日本獣医学会学術集会講演要旨集  155回-  188  -188  2013/03  [Not refereed][Not invited]
  
• 熱ショック誘導性の精細管腔内石灰沈着の発生機序と抑制因子の解析

  千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  155回-  188  -188  2013/03  [Not refereed][Not invited]
  
• MRLマウス肥満細胞は新生子期の卵形成に関与する

  中村鉄平, 市居修, 大塚沙織, 坂田侑子, 長崎健一, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  155回-  188  -188  2013/03  [Not refereed][Not invited]
  
• 糸球体腎炎モデルマウスにおける足細胞傷害の解析

  木村純平, 市居修, 大塚沙織, 佐々木隼人, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  155回-  187  -187  2013/03  [Not refereed][Not invited]
  
• Basic nephrology C.分子生物学 2.腎臓病のmiRNA解析

  市居修  Annual Review 腎臓  2013-  80  -87  2013/01/25  [Not refereed][Not invited]
  
• Basic nephrology 分子生物学 腎臓病のmiRNA解析

  市居 修  Annual Review腎臓  2013-  80  -87  2013/01  [Not refereed][Not invited]
   

  microRNA(miRNA)は短鎖のnon-codingRNAであり,主にmRNAを標的として転写後調節を担う.昨今の急進的なmiRNA研究によって,各疾患におけるmiRNAの病理学的意義やバイオマーカー・核酸治療ターゲットとしての可能性が徐々に明らかとなってきた.腎臓病領域においては,糖尿病性腎症や腎細胞癌におけるmiRNA研究が先行しており,局所病理発生に関与し,かつ患者の体液(血液,尿)特異的に出現するmiRNA種が網羅的発現解析をもとにリストアップされている.さらに,化学修飾アンチセンスmiRNA(antagomir)の生体投与は腎疾患モデル動物に一定の治療効果を示しており,miRNAが次世代の腎臓病診断・治療法として応用される未来は現実味を帯びてきている.(著者抄録)
• テリパラチド酢酸塩(56.5μg)投与後の血圧変動について

  城崎 和久, 奥田 亮宏, 市居 幸彦, 平岡 修治, 芳谷 和洋, 田中 康仁  Osteoporosis Japan  20-  (Suppl.1)  301  -301  2012/08  [Not refereed][Not invited]
  
• マウス消化管の発生に関する研究~どうして腸管は曲がるのか?~

  尾之内佐和, 市居修, 大塚沙織, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  154回-  173  -173  2012/08  [Not refereed][Not invited]
  
• 高温曝露後の精巣における減数分裂の進行と精細管腔内に出現する石灰沈着

  千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  154回-  176  -176  2012/08  [Not refereed][Not invited]
  
• 尿毒症物質インドキシル硫酸は腎糸球体上皮細胞傷害に関与する―芳香族炭化水素受容体のリガンド作用―

  市居修, 若新英史, 村上太一, 堀野太郎, LU Huiyan, TAKAHASHI Hideko, PATRICIA Zerfas, 大塚沙織, 橋本善春, 昆泰寛, KOPP Jeffrey  日本獣医学会学術集会講演要旨集  154回-  176  -176  2012/08  [Not refereed][Not invited]
  
• マレック病感染鶏由来腫瘍病変部における免疫抑制因子PD‐1/PD‐L1発現の形態学的解析

  村田史郎, 松山あゆ美, 伊勢崎政美, 高崎紗蘭, 市居修, 今内覚, 大橋和彦  日本獣医学会学術集会講演要旨集  154回-  234  -234  2012/08  [Not refereed][Not invited]
  
• 節足動物DNAのリボゾームRNA遺伝子ITS領域のサイズ分析による生物種同定の試み

  佐藤 福太郎, 遠藤 大二, 吉村 貴行, 伊東 拓也, 長 雄一, 浅川 満彦, 昆 泰寛, 市居 修, 大塚 沙織, 林 正信  獣医寄生虫学会誌  10-  (1-2)  50  -50  2012/03  [Not refereed][Not invited]
  
• MRL/MpJマウスの卵巣内肥満細胞出現に関与する遺伝的因子の解析

  中村鉄平, 坂田侑子, 大塚沙織, 市居修, 並木由佳, 長崎健一, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  153回-  194  -194  2012/03  [Not refereed][Not invited]
  
• 糸球体腎炎モデルマウスにおける尿中脱落細胞の動態解析

  木村純平, 市居修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆泰寛  解剖学雑誌  87-  (1)  5  -5  2012/03  [Not refereed][Not invited]
  
• マウス精巣における密着結合蛋白claudin‐3の局在および機能解析

  千原正尚, 市居修, 大塚沙織, 並木由佳, 池淵良洋, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  153回-  194  -194  2012/03  [Not refereed][Not invited]
  
• High-Resolution Linkage Mapping of the Rat Hooded Locus

  D. Torigoe, O. Ichii, D. Ruihua, T. Ohnaka, S. Okano, Y. Kon, N. Sasaki, T. Agui  JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE  50-  (5)  793  -793  2011/09  [Not refereed][Not invited]
  
• 節足動物DNAのリボゾームRNA遺伝子ITS領域のサイズ分析による生物種同定の試み

  佐藤福太郎, 遠藤大二, 吉村貴行, 伊東拓也, 長雄一, 浅川満彦, 昆泰寛, 市居修, 大塚沙織, 林正信  日本獣医学会学術集会講演要旨集  152nd-  207  2011/08/31  [Not refereed][Not invited]
  
• マウス涙腺炎における涙液を使った病態解析

  小千田圭吾, 市居修, 大塚沙織, 並木由佳, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  152回-  175  -175  2011/08  [Not refereed][Not invited]
  
• MRL/MpJマウスにおける精巣内卵細胞への分化開始時期の特定

  大塚沙織, 市居修, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆泰寛  日本獣医学会学術集会講演要旨集  152回-  168  -168  2011/08  [Not refereed][Not invited]
  
• マウス新生子卵巣に出現する肥満細胞の系統差解析

  中村鉄平, 市居修, 大塚沙織, 並木由佳, 坂田侑子, 長崎健一, 服部秀樹, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  152回-  172  -172  2011/08  [Not refereed][Not invited]
  
• マウス心筋発生過程に出現するTUNEL陽性細胞の解析

  長沼佑季, 市居修, 大塚沙織, 並木由佳, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  152回-  175  -175  2011/08  [Not refereed][Not invited]
  
• ラット頭巾斑遺伝子座の遺伝学的解析

  鳥越大輔, 市居修, 党瑞華, 佐々木宣哉, 昆泰寛, 安居院高志  日本実験動物学会総会講演要旨集  58th-  173  2011/05/12  [Not refereed][Not invited]
  
• 129+Ter/Svマウスの遺伝的背景は腎糸球体硬化症に抵抗性である

  西野 智博, 佐々木 宣哉, 長崎 健一, 市居 修, 昆 泰寛, 安居院 高志  日本獣医学会学術集会講演要旨集  151回-  276  -276  2011/03  [Not refereed][Not invited]
  
• マウス血液精巣関門関連分子の局在と動態―claudin‐3,‐11,occludin,ZO‐1の発現解析―

  千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛  解剖学雑誌  86-  (1)  12  -12  2011/03  [Not refereed][Not invited]
  
• MRLマウス新生子卵巣における肥満細胞の出現

  中村鉄平, 市居修, 大塚沙織, 並木由佳, 長崎健一, 服部秀樹, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  151回-  190  -190  2011/03  [Not refereed][Not invited]
  
• 腎症候性出血熱の致死的感染モデルの開発とその病態解析

  瀬戸隆弘, 吉川佳佑, 真田崇弘, SAASA Ngonda, 尾崎由佳, 市居修, 好井健太朗, 昆泰寛, 苅和宏明  日本獣医学会学術集会講演要旨集  151回-  245  -245  2011/03  [Not refereed][Not invited]
  
• 節足動物DNAのITS領域サイズ分析による生物種同定の試み

  遠藤大二, 吉村貴行, 佐藤福太郎, 伊東拓也, 長雄一, 浅川満彦, 昆泰寛, 市居修, 大塚沙織, 林正信  日本獣医学会学術集会講演要旨集  151st-  220  2011/03/01  [Not refereed][Not invited]
  
• 慢性腎臓病におけるmicroRNAの発現解析―腎間質病変に関与するmi‐R146a―

  市居修, 大塚沙織, 並木由佳, 佐々木宣哉, 橋本善春, 遠藤大二, 昆泰寛  日本獣医学会学術集会講演要旨集  151回-  189  -189  2011/03  [Not refereed][Not invited]
  
• 129^+Ter/Svマウスの遺伝的背景は腎糸球体硬化症に抵抗性である

  西野智博, 佐々木宣哉, 長崎健一, 市居修, 昆泰寛, 安居院高志  日本獣医学会学術集会講演要旨集  151回-  276  -276  2011/03  [Not refereed][Not invited]
  
• MRL/MpJマウスにおける卵巣網由来卵巣嚢腫の経時的観察

  李愼曉, 大塚沙織, 市居修, 並木由佳, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  151回-  190  -190  2011/03  [Not refereed][Not invited]
  
• Cytoarchitectural differences of myoepithelial cells among goat major salivary glands (vol 34, pg 557, 2010)

  Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon  VETERINARY RESEARCH COMMUNICATIONS  34-  (8)  727  -727  2010/12  [Not refereed][Not invited]
  
• ヤギの大唾液腺における離乳前・後期のアクアポリンファミリー発現の比較解析(Comparative analysis of the expression of aquaporin family between pre- and post-weaning periods in goat major salivary glands)

  Yaser Elewa, 市居 修, 大塚 沙織, 金澤 智則, 李 愼曉, 並木 由佳, 昆 泰寛, 橋本 善春  日本獣医学会学術集会講演要旨集  150回-  160  -160  2010/09  [Not refereed][Not invited]
  
• MRLマウスの精巣内卵細胞出現に関与する遺伝的因子の解析

  大塚沙織, 市居修, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆泰寛  日本獣医学会学術集会講演要旨集  150回-  154  -154  2010/09  [Not refereed][Not invited]
  
• DBA/2マウスの腎臓における遠位尿細管上皮傷害―多発性嚢胞腎の早期病変としての可能性

  市居修, 大塚沙織, 矢吹映, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆泰寛  日本獣医学会学術集会講演要旨集  150回-  160  -160  2010/09  [Not refereed][Not invited]
  
• 尿中脱落細胞の動態は腎疾患の増悪と相関する―糸球体腎炎モデルの解析

  木村純平, 市居修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  150回-  160  -160  2010/09  [Not refereed][Not invited]
  
• ヤギ耳下腺の年齢関連の構造変化(Age-related structural changes of parotid salivary glands in goat)

  Elewa Yaser, 橋本 善春, 市居 修, 大塚 沙織, 金澤 智則, 昆 泰寛  日本獣医学会学術集会講演要旨集  149回-  211  -211  2010/03  [Not refereed][Not invited]
  
• マウスのネフロン形成過程における間葉‐上皮転換(MET)の解析

  金澤智則, 大塚沙織, 市居修, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  149回-  216  -216  2010/03  [Not refereed][Not invited]
  
• イヌおよびネコの腎疾患における病態差―腎機能とスリット膜関連分子の動態―

  市居修, 矢吹映, 佐々木宣哉, 大田寛, 滝口満喜, 大塚沙織, 橋本善春, 遠藤大二, 昆泰寛  日本獣医学会学術集会講演要旨集  149回-  213  -213  2010/03  [Not refereed][Not invited]
  
• MRLマウス胎子精巣内における減数分裂開始と精巣内卵細胞の出現

  大塚沙織, 市居修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆泰寛  日本獣医学会学術集会講演要旨集  149回-  213  -213  2010/03  [Not refereed][Not invited]
  
• 慢性腎臓病は制御可能か?―疾患モデル動物にターゲット因子を求めて―

  市居修  北海道獣医師会雑誌  53-  (11)  638  -644  2009/11  [Not refereed][Not invited]
  
• (DBA/2×C57BL/6)F2交雑マウスに出現する水腎症

  市居 修, 昆 泰寛, 佐々木 宣哉, 矢吹 映, 大塚 沙織, 橋本 善春, 遠藤 大二  日本獣医学会学術集会講演要旨集  148回-  153  -153  2009/09  [Not refereed][Not invited]
  
• マウス精子形成過程における血液精巣関門構成分子の動態

  千原正尚, 大塚沙織, 市居修, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  148回-  155  -155  2009/09  [Not refereed][Not invited]
  
• (DBA/2x C57BL/6)F2交雑マウスに出現する水腎症

  市居修, 昆泰寛, 佐々木宣哉, 矢吹映, 大塚沙織, 橋本善春, 遠藤大二  日本獣医学会学術集会講演要旨集  148回-  153  -153  2009/09  [Not refereed][Not invited]
  
• 腎疾患の新しい診断指標―Interleukin 1 family,member 6は尿細管傷害マーカーになり得る―

  市居修, 昆泰寛, 佐々木宣哉, 橋本善春, 大田寛, 滝口満喜, 矢吹映, 遠藤大二  日本獣医学会学術集会講演要旨集  147回-  79  -79  2009/03  [Not refereed][Not invited]
  
• MRL/MpJマウスに出現する精巣内卵細胞の解析

  大塚沙織, 市居修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆泰寛  日本顕微鏡学会北海道支部学術講演会講演要旨集  2009-  11  2009  [Not refereed][Not invited]
  
• マウス精子形成過程における血液精巣関門構成分子の動態

  千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛  日本顕微鏡学会北海道支部学術講演会講演要旨集  2009-  12  2009  [Not refereed][Not invited]
  
• テンシン2遺伝子の糸球体上皮細胞における機能解析

  佐々木宣哉, 市居修, 昆泰寛, 安居院高志  日本獣医学会学術集会講演要旨集  146回-  300  -300  2008/09  [Not refereed][Not invited]
  
• Interferon activated gene200(Ifi200)遺伝子群と自己免疫性糸球体腎炎の関連性

  市居修, 上川昭博, 佐々木宣哉, 今野明弘, 遠藤大二, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  146回-  147  -147  2008/09  [Not refereed][Not invited]
  
• 性腺摘出が自己免疫性糸球体腎炎の病態に与える影響について

  市居修, 今野明弘, 佐々木宣哉, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  145回-  161  -161  2008/03  [Not refereed][Not invited]
  
• 自己免疫性糸球体腎炎とFc gamma receptor III(FcγRIII)の関連性について

  市居修, 今野明弘, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  144回-  33  -33  2007/08  [Not refereed][Not invited]
  
• 齧歯目における腎臓の短および長ループネフロンの比率の種差(Species Specific Differences in the Ratio of Short to Long Loop Nephrons in the Kidneys of Laboratory Rodents)

  市居 修, 矢吹 映, 小嶋 敏慶, 松元 光春, 鈴木 秀作  Experimental Animals  55-  (5)  473  -476  2006/10  [Not refereed][Not invited]
   

  The ratio of short to long loop nephrons (SLNs and LLNs, respectively) in laboratory rodents (mice, rats, hamsters, gerbils, and guinea pigs) was investigated using the air cast method. In mice and rats, the percentage of SLNs was significantly higher than that of LLNs, while in hamsters and gerbils, the reverse was true (% of LLNs >% of SLNs). In guinea pigs, no significant difference in the percentages of LLNs and SLNs was noted.
• Species specific differences in the ratio of short to long loop nephrons in the kidneys of laboratory rodents.

  Osamu Ichii, Akira Yabuki, Toshimichi Ojima, Mitsuharu Matsumoto, Shusaku Suzuki  Experimental animals  55-  (5)  473  -6  2006/10  [Refereed][Not invited]
   

  The ratio of short to long loop nephrons (SLNs and LLNs, respectively) in laboratory rodents (mice, rats, hamsters, gerbils, and guinea pigs) was investigated using the air cast method. In mice and rats, the percentage of SLNs was significantly higher than that of LLNs, while in hamsters and gerbils, the reverse was true (% of LLNs >% of SLNs). In guinea pigs, no significant difference in the percentages of LLNs and SLNs was noted.
• MRL/MpJマウス由来コンジェニックマウスに出現する自己免疫性糸球体腎炎

  市居修, 今野明弘, 橋本善春, 昆泰寛  日本獣医学会学術集会講演要旨集  142回-  40  -40  2006/08  [Not refereed][Not invited]
  
• 齧歯目の腎臓の組織構造における種差(Rodent Renal Structure Differs among Species)

  市居 修, 矢吹 映, 小嶋 敏慶, 松元 光春, 鈴木 秀作  The Journal of Veterinary Medical Science  68-  (5)  439  -445  2006/05  [Not refereed][Not invited]
   

  In the present study, we histologically and morphometrically investigated species differences in renal structure using laboratory rodents (mice, gerbils, hamsters, rats, and guinea pigs). Morphometric parameters were as follows, 1) diameter of the cortical renal corpuscles, 2) diameter of the juxtamedullary renal corpuscles, 3) percentage of the renal corpuscles with a cuboidal parietal layer, 4) number of nuclei in proximal convoluted tubules (PCTs) per unit area of cortex. 5) semi-quantitative score of the periodic acid-Schiff (PAS) positive granules in PCTs, and 6) semi-quantitative score of the PAS-positive granules in proximal straight tubules (PSTs). Significant species differences were detected for each parameter, and particularly severe differences were observed in the PAS-positive granules of PCTs and PSTs. Granular scores varied among species and sexes. Vacuolar structures that did not stain with PAS or hematoxylin-eosin were observed in the renal proximal tubules. The appearance and localization of these vacuolar structures differed remarkably between species and sexes.
• Rodent renal structure differs among species

  O Ichii, A Yabuki, T Ojima, M Matsumoto, S Suzuki  JOURNAL OF VETERINARY MEDICAL SCIENCE  68-  (5)  439  -445  2006/05  [Not refereed][Not invited]
   

  In the present study, we histologically and morphometrically investigated species differences in renal structure using laboratory rodents (mice, gerbils, hamsters, rats, and guinea pigs). Morphometric parameters were as follows, 1) diameter of the cortical renal corpuscles, 2) diameter of the juxtamedullary renal corpuscles, 3) percentage of the renal corpuscles with a cuboidal parietal layer, 4) number of nuclei in proximal convoluted tubules (PCTs) per unit area of cortex. 5) semi-quantitative score of the periodic acid-Schiff (PAS) positive granules in PCTs, and 6) semi-quantitative score of the PAS-positive granules in proximal straight tubules (PSTs). Significant species differences were detected for each parameter, and particularly severe differences were observed in the PAS-positive granules of PCTs and PSTs. Granular scores varied among species and sexes. Vacuolar structures that did not stain with PAS or hematoxylin-eosin were observed in the renal proximal tubules. The appearance and localization of these vacuolar structures differed remarkably between species and sexes.
• 齧歯目の腎臓における種差 ネフロン長,GFR調節因子,水チャネルおよびナトリウムポンプについて

  市居 修, 矢吹 映, 小嶋 敏慶, 松元 光春, 鈴木 秀作  日本獣医学会学術集会講演要旨集  140回-  46  -46  2005/08  [Not refereed][Not invited]
  
• げっ歯目の腎臓における種差‐ネフロン長,GFR調節因子,水チャネルおよびナトリウムポンプについて‐

  市居修, 矢吹映, 小嶋敏慶, 松元光春, 鈴木秀作  日本獣医学会学術集会講演要旨集  140回-  46  -46  2005/08  [Not refereed][Not invited]
  

Awards & Honors

• 2018/09 The Japanese Society of Veterinary Science The Japanese Society of Veterinary Science Award
   Studies on the novel marker molecules for kidney diseases and their application to clinical veterinary medicine 

  受賞者: ICHII Osamu
• 2017/03 Kazato Research Foundation Kazato Research Encouragement Prize
   走査型電子顕微鏡の応用的手法による腎臓病理解析法の革新 

  受賞者: ICHII Osamu
• 2013/03 Japanese Association of Veterinary Anatomists Best poster award in Japanese Association of Veterinary Anatomists
   腎臓病のmicroRNA解析―動物種共通のバイオマーカー開発を目指して― 

  受賞者: Osamu ICHII
• 2011/04 Leave a Nest Co.,ltd. Leave a Nest Toray award
   種の壁を越えた尿中microRNAバイオマーカーの開発 

  受賞者: Osamu ICHII
• 2009/03 Japanese Society of Veterinary Science Veterinary Science Young Investigator Award
   腎疾患の新しい診断指標－Interleukin 1 family,member 6 は尿細管傷害マーカーになり得る－ 

  受賞者: Osamu ICHII
• 2009/03 Japanese Society of Veterinary Science Award from the chairman
   腎疾患の新しい診断指標－Interleukin 1 family,member 6 は尿細管傷害マーカーになり得る－ 

  受賞者: Osamu ICHII
• 2008/03 Japanese Association of Veterinary Anatomists Best presentation award in Japanese Association of Veterinary Anatomists
   性腺摘出が自己免疫性糸球体腎炎の病態に与える影響について 

  受賞者: Osamu ICHII
• 2007/09 Japanese Association of Veterinary Anatomists Award in Japanese Association of Veterinary Anatomists
   自己免疫性糸球体腎炎とFc gamma receptor III (Fcgr3)の関連性について 

  受賞者: Osamu ICHII

Research Grants & Projects

• ウシのリンパ陰部輪の発見 ―粘膜ワクチン投与部位としての有効性―

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  Date (from‐to) : 2019/04 -2024/03 

  Author : 昆 泰寛, エレワ ヤセル, 市居 修, 中村 鉄平
• 尿路関連リンパ組織の発見から展開する新たな腎泌尿器免疫学

  日本学術振興会：科学研究費助成事業 挑戦的研究(萌芽)

  Date (from‐to) : 2019/06 -2022/03 

  Author : 市居 修, 昆 泰寛, エレワ ヤセル, 中村 鉄平
• Make Eve from Adam - challenge of animal creation by using only male genome -

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Challenging Research (Exploratory)

  Date (from‐to) : 2019/06 -2022/03 

  Author : 昆 泰寛, エレワ ヤセル, 市居 修, 中村 鉄平
• ノンコーディングRNAとエクソソーム機能解析から腎臓病の新規治療法を開発する

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  Date (from‐to) : 2019/04 -2022/03 

  Author : 堀野 太郎, 市居 修
• Liquid microanatomy to discover the renal injury markers from exosome-derived microRNAs in primitive urine

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2018/04 -2021/03 

  Author : 市居 修, 昆 泰寛

   

  腎臓病の増加は動物やヒトの未来を脅かしている。新規腎障害マーカーの確立は、腎臓病の次世代バイオマーカー診断技術 “Liquid Biopsy” の実現に必要である。本研究では、早期検出・高特異性を達成する新たな腎障害マーカーを、尿よりも早く腎病理を反映する“原尿”からみつける。具体的には、腎障害初期のモデル動物の腎組織切片から、Laser-Microdissection技術で “尿細管内の原尿”を集める。 まず本年度では、モデル動物としてマウスを用い、腎臓内エクソソームの局在解析を進めてきた。健常マウスの腎臓を用い、CD9をエクソソームマーカーとして免疫染色を行ったところ、CD9陽性反応は尿細管上皮細胞の細胞質ならびに尿細管間質の単核細胞の細胞表面に認められた。また、腎障害モデルマウスでは、拡張した一部の尿細管の管腔内にCD9陽性の顆粒状構造が認められた。現在、このCD9陽性顆粒状構造を免疫電顕法で可視化し、その超微形態を透過型電子顕微鏡ならびに走査型電子顕微鏡を用いて解析している。 一方、原尿に放出されたエクソソームの運命として、尿への出現に加えて、尿細管、集合管あるいは尿路移行上皮からの再吸収も想定しており、本年度は特に腎盤の解析を進めてきた。腎臓深部の腎盤の移行上皮直下には線維芽細胞に加えて、T細胞やB細胞などの免疫細胞が配置されており、腎盤内の尿からエクソソームや抗原を吸収することで、免疫学的な情報を受けとる可能性にも着目している。
• イヌの新規ゲノムワイドDNAメチル化解析：腫瘍性疾患特異的DNAメチル化の同定

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  Date (from‐to) : 2018/04 -2021/03 

  Author : 山崎 淳平, 市居 修

   

  イヌの悪性黒色腫におけるエピジェネティクス特にDNAメチル化に関し、次世代シークエンサーを用いて新たな知見を得ることによってイヌの悪性黒色腫のメカニズムを解明することにつなげるため、平成30年度は以下の項目について検討を行った。 DREAM（Digital Restriction Enzyme Analysis of Methylation）法によるゲノムワイドなDNAメチル化の変化の検出 申請者らが樹立したイヌ悪性黒色腫腫細胞株4株よりDNAを抽出、制限酵素処理を行った後、アダプター結合からPCRを行うことによって、次世代シークエンサーに最適な目的のサイズを持ったライブラリを作製した。次世代シークエンサーによる解析を行ったところ、全ての検体において約125,000～180,000箇所のCpGサイトのDNAメチル化の定量的な解析が可能であった。実際にこれらの配列を用いて解析をおこなったところ、DNAメチル化状態の類似性によって分類した結果、悪性黒色腫細胞株群と正常組織群の区別が可能であり、また、悪性黒色腫細胞株間においても異なるDNAメチル化状態が存在することが示された。さらに、各々の悪性黒色腫細胞株において3,000～5,000箇所の高メチル化部位が発見された。これらのうち、特に高メチル化部位の近傍には腫瘍に関連すると考えられる遺伝子が認められた。現在この結果に関して、論文投稿中である。 さらに、イヌの悪性黒色腫自然発症例16例についても同様の解析・検討を行ったところ、症例によって異なるゲノムワイドなDNAメチル化の変化が検出され、これを用いてグループ分けすることによって、臨床的なパラメータと独立した予後因子の同定を試みている。
• イヌの新規ゲノムワイドDNAメチル化解析：腫瘍性疾患特異的DNAメチル化の同定

  文部科学省：科学研究費補助金(基盤(C))

  Date (from‐to) : 2018/04 -2021/03 

  Author : 山崎 淳平
• 体液顕微解剖の実践：原尿中エクソソーム由来マイクロＲＮＡに腎障害マーカーを求めて

  文部科学省：科学研究費補助金(基盤(B))

  Date (from‐to) : 2018/04 -2021/03 

  Author : 市居 修
• ウシの各種感染性疾患におけるバイオフィルムの機能解析

  栗林育英学術財団：研究助成

  Date (from‐to) : 2017/06 -2019/03 

  Author : 市居 修
• 産業動物の粘膜関連リンパ組織の探索―より効果的なワクチン接種部位を求めて―

  公益財団法人 伊藤記念財団：研究助成

  Date (from‐to) : 2017/06 -2019/03 

  Author : 市居 修
• 走査型電子顕微鏡の応用的手法による腎臓病理解析法の革新

  Kazato Research Foundation：Kazato Research Encouragement Prize

  Date (from‐to) : 2017/04 -2019/03 

  Author : ICHII Osamu
• 新たなlgA腎症モデル動物の発見とその病態解析－カスパーゼ３の原因遺伝子としての役割－

  株式会社ケー・エー・シー：創立40周年記念 研究助成

  Date (from‐to) : 2018/04 

  Author : 市居 修
• Urinary exosome-derived microRNAs in companion animals:application for kidney injury markers

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

  Date (from‐to) : 2015/04 -2018/03 

  Author : Osamu Ichii

   

  The patients with kidney disease are increasing in both companion animals and human. Early diagnosis is a crucial therapeutic strategy for non-regenerative kidney. In this study, we tried to find the biomarker candidates from urinary exosome-derived microRNA to develop the non-invasive “Liquid Biopsy”. In the comprehensive expression analysis and pathological analysis of animals, we identified miR-26a as a candidate for renal glomerular injury marker. Further, several animal species commonly expressed miR-26a in their glomeruli, indicating a possibility of animal species-crossing biomarker. Further, for the application of miRNA to clinical area, we need to clarify further miRNA marker candidates, their correlations with renal function, their dynamics at early disease stage, and their pathological relations with tubulointerstitial lesions.
• Screening of candidate genes associating with the progression of chronic kidney disease in mice

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

  Date (from‐to) : 2015/04 -2017/03 

  Author : Ichii Osamu, HORINO TARO

   

  Chronic kidney disease (CKD) is a serious problem from the points of increase of the patients with CKD as well as medical economy. In the present study, we discovered the candidate locus associating with the progression of CKD in DBA/2 mouse inbred strain. We named this locus as DBA/2 renal cyst“drecy”. From the pathological analysis, drecy locus related to the alternation of molecules associating with the transportations of ion or vesicle and cell-adhesion in the epithelial cells of distal tubules. We considered that these alternations would lead the abnormal phenotypes of distal tubules, including cyst formation. Furthermore, gene expression analysis suggested that the genes encoded on DBA/2-type chromosome 12 (D12Mit182-83), in particular Greb1, associate with the progression of these phenotypes.
• Investigation of pathological mechanisms for diagnostic and treatment strategy of glomerulonephropathy in dogs and cats

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2013/04 -2016/03 

  Author : Yabuki Akira, YAMATO OSAMU, ICHII OSAMU

   

  The aim of the present study was to clarify the pathological mechanisms of glomerulonephropathy in dogs and cats, especially in dogs. In pathologically, interstitial fibrosis was closely related with the deterioration of renal functions. Changes of several factors including carbohydrate chains, nephrin, and ghrelin were demonstrated in the cases with glomerulonephropathy, especially immune-complex mediated glomerulonephritis (ICGN). However, no common changes were detected in the course of ICGN, and this finding was thought to be reflected the complexity of pathological changes and clinical features of this disease.
• Development of next-generation biomarkers for chronic kidney disease: MicroRNAs in the urine of companion animals

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

  Date (from‐to) : 2012/04 -2015/03 

  Author : ICHII Osamu

   

  Recently, the numbers of human and animal patients with chronic kidney disease (CKD) have been increasing. It is crucial to diagnose and start treatment as an early therapeutic strategy for CKD. In this study, several animals were analyzed in order to use microRNAs as an early diagnostic tool for CKD. Specific microRNAs that indicated the progression of CKD were detected in the urine. These microRNAs were expressed in the kidneys of mice, as well as in those of dogs, cats, and humans, and could be used as an early diagnostic tool (biomarkers) for CKD.
• Novel pathological mechanisms and therapy strategy for canine and feline kidney diseases: association with COX and RA

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2010 -2012 

  Author : YABUKI Akira, YAMATO Osamu, ICHII Osamu, HOSAKA Yoshinao, MIZUKAMI Keijiro, MITANI Sawane, TOMINAGA Naomi

   

  In the present study, we investigated pathological mechanisms of kidney diseases in dogs and cats, especially involvement of cyclooxygenase (COX) and renin-angiotensin (RA) system. Results from pathological investigation demonstrated close and complicated relationships between renal COX and RA system and progression of the kidney diseases, and such mechanisms were clearly differentbetween dogs and cats. Investigation using model mice demonstrated the renoprotective effect of piroxicam (COX inhibitor), and it was suggested that such renoprotective effect was induced from the downregulation of TGF-beta.
• 種の壁を越えた尿中microRNAバイオマーカーの開発－慢性腎臓病の非侵襲的早期診断法への応用－

  リバネス：リバネス研究費

  Date (from‐to) : 2012 

  Author : 市居 修
• Development of innovative method for diagnosing renal disease -Urinary Molecular Profiling-

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up

  Date (from‐to) : 2009 -2010 

  Author : ICHII Osamu

   

  This study clarified that the renal parenchymal cells were dropped into urine in renal pathological conditions. The quantitative and qualitative urinary cellular patterns correlated with the deteriorations of renal pathology and function in renal disease models and companion animals. Importantly, these urinary cells could be detected by molecular biological methods targeting mRNA and microRNA in urine. These data indicated the possibility that the urinary tests based on the detections of urinary cells, entitled "Urinary Molecular Profiling" in the present study, could be noninvasive diagnosis methods for renal disease.
• 自己免疫性糸球体腎炎モデルの解析

  日本学術振興会：科学研究費助成事業 特別研究員奨励費

  Date (from‐to) : 2007 -2008 

  Author : 市居 修

   

  自己免疫性糸球体腎炎(AGN)は主として血中を循環する免疫複合体が糸球体に沈着することで発症する。本研究では本症のモデル動物を確立し、原因因子の探索ならびに新規診断および治療法への応用を目的としている。前年度では自己免疫疾患モデルであるMRLマウス由来第1染色体テロメア領域を有するB6.MRLc1(82-100)コンジェニックマウスを作出し、AGNモデルとして有用であることを報してきた。 本年度では、新たに作出した3系統のコンジェニックマウス(B6.MRLc1(82-86,92-100,100))について解析し、B6.MRLc1(92-100)でAGN発症を確認した。すなわち、AGN原因遺伝子の存在領域は第1染色体92-100cMに狭められた。当領域の原因遺伝子候補として、抑制型免疫複合体受容体IIB(FcγRIIB)および活性化型FcγRIIIの発現をB6.MRLc1(92-100)の腎臓、脾臓および胸腺で検討した。両蛋白は腎糸球体メサンギウム領域に局在し、上記3臓器でFcγIII/FcγRIIB遺伝子発現比の上昇が認められた。これより、第1染色体約92.3cMに存在するFcγR遺伝子のバランス変化がAGN発症に深く関与することが強く示唆された。 次に、B6.MRLc1(82-100)由来AGNの雌雄差に着目し、性腺摘出術を施し解析した。その結果、去勢雌は正常化したが、去勢雄のAGNは悪化した。このことから、B6.MRLc1(82-100)のAGNの雌雄差は、雄性ホルモンの病態抑制作用の影響を強く受けることが示唆された。 更に、AGN増悪因子同定のため、B6.MRLc1(82-100)の腎臓で発現上昇する炎症性メディエーターをPCRarray法で網羅的に解析した。結果、B6.MRLc1(82-100)の腎臓でCXCL5およびIL-1F6の遺伝子発現上昇が認められ、前者は糸球体上皮細胞に、後者は遠位尿細管から集合管に局在した。このことから、CXCL5およびIL-1F6はそれぞれ糸球体および尿細管間質病変の増悪因子として重要な役割を果たすことが示唆された。

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• 新薬開発や再生医療促進への寄与を目指し実験動物学分野の研究に助成

  Date : 2018/05

  Writer: Other than myself

  Program, newspaper magazine: 薬事日報メディカル版

  Paper
• 40周年記念 研究助成 治療薬開発へ貢献目指す

  Date : 2018/04

  Program, newspaper magazine: 薬事日報

  Paper
• 見て、触って、学ぶ。最古にして最先端の学問、解剖学

  Date : 2018/01

  Writer: Other than myself

  Program, newspaper magazine: いいね！Hokudai

  Internet